枯草杆菌生物素操纵子基因的克隆、序列改造及功能表达研究
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摘要
利用基因工程技术生产生物素是国际上高技术竞争的又一热点。由于生物素能够提高家畜胴体质量和改善肉质，提高家畜繁殖力，是家畜品种性能正常发挥所必需的物质。目前，生物素只能通过化学合成方法获得，且均从国外进口，价格昂贵，制约了我国畜牧科技和产业的发展。随着基因工程技术的兴起，人们开始转向生物素生物合成的研究。生物合成方法可以进行生物素的专一性合成，克服了化学合成法收率低，不能专一性合成，需经高成本化学拆分过程才能获得d-生物素的弊端，可使生物素的生产成本降低，从而提高畜牧业的经济效益。我国尚无这方面的研究，因此，开展本研究具有重要的理论意义和经济价值。
本研究以枯草杆菌ASl.1094菌株为研究材料，克隆了生物素操纵子基因，并对基因序列进行改造。而后对改造后的生物素操纵子基因进行了功能表达检测及bioW与bioB基因的诱导表达。旨在探索如何提高生物素操纵子基因的表达效率，为该操纵子基因的高效表达提供可行的研究路线和理论依据。并构建了可商业化操作的研究素材，为以后的研究提供探索性经验。本论文主要作了以下几方面的研究：
1．大片段基因组DNA的提取
为了获得用于PCR扩增(长距离PCR扩增和分段PCR扩增)的高纯度、大片段(至少为PCR产物长度的4倍)的DNA模板，应用三种方法：低熔点琼脂糖包埋法，SDS-蛋白酶K-酚氯仿抽提法和细菌基因组DNA提取试剂盒法，分别提取获得了枯草杆菌基因组DNA，并对3种方法的操作程序进行了不同程度的改进，结果表明：低熔点琼脂糖包埋法提取的基因组DNA片段明显大于后两种方法，采用0.5％琼脂糖凝胶电泳3h，仍然跑不出加样孔。将该方法提取的基因组DNA稀释100倍作为模板，采用长距离PCR方法，获得了枯草杆菌生物素操纵子基因全长。说明以低熔点琼脂糖包埋法提取枯草杆菌基因组DNA，并获得较大的DNA片段，是完全可行的。
2．枯草杆菌生物素操纵子基因的克隆
将枯草杆菌基因组DNA稀释后，通过PCR反应条件的优化，分别扩增得到了生物素操纵子基因的长距离PCR产物(10.3kb)和3个分段PCR产物。而后采用TA克隆方法，经PCR产物的纯化、两端加A、pGEM-T载体连接、转化大肠杆菌、阳性克隆的酶切鉴定及重组质粒测序，分别获得了生物素操纵子基因3个片段(bio-1、bio-2、bio-3)的克隆质粒。应用分子生物学软件对测序结果进行了分析，并与Genebank中枯草杆菌168菌株的生物素操纵子基因序列进行了对比分析：共有12个碱基差异，且7个碱基导致了氨基酸变异，但未出现移码突变现象。
利用长距离PCR扩增引物为测序引物，利用PCR产物直接测序法，在长距离PCR产物两侧各测了1个反应，并与Genebank中168菌株序列进行了对比分析：两个菌株的序列基本吻合，只有1个碱基的差异。
通过2种方法对3个基因片段的转化效率比较和质粒浓度的测定(重复多次)，
结果表明:biow基因作为大肠杆菌的外源基因，插入高拷贝的pGEM一T载体中，重
组后的质粒具有不稳定性。
3.枯草杆菌部分基因组文库的构建及筛选
首先，通过对枯草杆菌生物素操纵子基因序列和基因组序列的分析，选择刀。脚Hl
和KPnl位点。用这2个内切酶分别将基因组DNA和BluescriPt SKM13载体完全酶
切消化，分别纯化回收(酶切的基因组DNA回收4.3一7kb间的片段)，并用几DNA
Ligase连接，转化大肠杆菌DHS。。
应用PCR快检法对构建的枯草杆菌部分基因组文库进行了筛选，共检测了250
个菌落，得到了3个阳性克隆子，经酶切鉴定和测序，获得了生物素操纵子5.Ikb的
BamHI一KPnl亚克隆片段。测序结果表明:ASI .1 094菌株与168菌株bioAFDB基因
序列完全一致，9个差异碱基是由于PCR扩增导致的。
枯草杆菌生物素操纵子基因4个亚克隆序列的测序结果证实，ASI .1 094菌株和
168菌株生物素操纵子基因序列是完全一致的(见附件1)。
4.枯草杆菌生物素操纵子基因序列的改造
基因序列改造的关键是删除bioB与biof基因间的终止子，在Bowe:等(1 996)
[’97]序列研究分析的基础上，设计一对PcR引物，以bi。一2片段克隆质粒为模板，采
用Skip PCR方法，得到了约4.3kb产物，以TA克隆方式，插入pGEM一T载体中。将
经鉴定的阳性克隆质粒进行测序，结果表明:bioB与biol基因间的5 lbp的终止子序
列已被删除。在基因序列分析的基础上，采用特征酶酶切的方式，还删除了生物素操
纵子基因上、下游与生物合成无关的序列。并将改造后的枯草杆菌生物素操纵子基因
的3个片段依次插入pGEM一T载体中。并经binw、bioB及biol基因3’端的引物进
行PCR扩增和重组质粒酶切鉴定而得到证实。
5.改造后的生物素操纵子基因的功能表达检测及biow和 bioB基因的诱导表达
为了检测改造后的生物素操纵子基因是否能够正常表达，我们利用生物素是细菌
生长的必需物质这一特点，用4种大肠杆菌生物素缺陷株(R874、R875、R877、R879)
经遗传互补分析表明:改造后的生物素操纵子中的bioA、binF、bioD、bioB4个基因
均能够表达。因此，bioB与biof基因间终止子序列的删除，不影响基因的表达。
同时也证实，虽然所克隆的枯草?
It was one of hot spots of high-technologic competition that biotin was produced by using genetically engineered technology. It could improve carcass quality meat quality, reproductive ability of livestock, and was indispensible matter for normal elaboration of livestock's varietal performance.Up till now, biotin could only be gained by the method of chemical synthesis and only imported from the foreign countries,and its price was very expensive and seriously restricted the development of our country's animal husbandry. Alongside rising of genetically engineered technology, the people begined to research biotin biosynthesis. The biosynthetic method could carry on the specific synthesis of biotin and overcome the low yield, nonspecific synthesis and nessary use of the chemical separation for chemically synthetic method.This method could reduce manufacturing cost of biotin, and improved economic benefits of animal husbandry. The use of this method had importantly theoretical meaning and economic value.
Used As 1.1094 strain of Bacillus subtilis as researched material, the structural genes of biotin operon(bio operon) were cloned, and its sequence were engineered. Then the engineered genes of bio operon were carried on testing of the functional expression, and bioW & bioB gene were induced to express. This experiment probed how to improve the expression efficiency of the structural genes of bio operon, and provided the feasibly researched route and scientifically theoretical foundation. For highly efficient expression of the structural genes of bio operon, a lot of researched materials were constructed which could commercially operated in this experiment and these materials provided some explored experience and reference materials for future research. The study mainly carried on several research followed: 1. Extraction of large-fragment genomic DNA
In order to gain DNA template of PCR amplification (Long PCR amplification and salvage PCR amplification) which was high purity and large fragment, three methods were used to extract genomic DNA of Bacillus subtilis, i.e. low melting-point agarose embedding method, SDS-Proteinase K-Phenol Chloroform extraction method and bacterial genomic DNA extraction kit method. The genomic DNA of Bacillus subtilis were gained
by these methods, and the operated programs of the methods were improved. The results showed that the genomic DNA extracted by low melting-point agarose embedding method were obviously biggest than that of another two methods. Used the genomic DNA extracted by low melting-point agarose embedding method as PCR template, the full length of structural genes of Bacillus subtilis bio operon were gained by long PCR method. The results also explained that it was feasible that the genomic DNA of Bacillus subtilis were extracted and gained large DNA fragments by low melting-point agarose embedding method.
2. Cloning of structural genes of Bacillus subtilis bio operon
Diluted the genomic DNA of Bacillus subtilis as the template, long PCR product (10.3kb) and three salvage PCR products were separately gained by optimization of reaction conditions of PCR. Then used TA cloning method, The plasmids of three fragments( bio-1 bio-2 bio-3) of structural genes of Bacillus subtilis bio operon were gained by the purity of PCR products adding A in the two side of the products ligation with pGEM-T vector transformed Escherichia col identification and sequencing of recombinant plasmid. Contrasting analysis with the genes sequence of Bacillus subtilis 168 strain's bio operon, the sequence of bio operon of As 1.1094 strain had 12 bases difference with that of 168 train,and 7 bases caused variation of amino acid.
Used long PCR primers as sequencing primer, the two sides of sequence of the long PCR product were separately sequenced one reaction by the direct sequencing method of PCR products, and the sequencing sequence were carried on constrasted analysis with sequence of 168 strain in Genebank. The results showed that the sequence of two strains basically coincided but
本研究以枯草杆菌ASl.1094菌株为研究材料，克隆了生物素操纵子基因，并对基因序列进行改造。而后对改造后的生物素操纵子基因进行了功能表达检测及bioW与bioB基因的诱导表达。旨在探索如何提高生物素操纵子基因的表达效率，为该操纵子基因的高效表达提供可行的研究路线和理论依据。并构建了可商业化操作的研究素材，为以后的研究提供探索性经验。本论文主要作了以下几方面的研究：
1．大片段基因组DNA的提取
为了获得用于PCR扩增(长距离PCR扩增和分段PCR扩增)的高纯度、大片段(至少为PCR产物长度的4倍)的DNA模板，应用三种方法：低熔点琼脂糖包埋法，SDS-蛋白酶K-酚氯仿抽提法和细菌基因组DNA提取试剂盒法，分别提取获得了枯草杆菌基因组DNA，并对3种方法的操作程序进行了不同程度的改进，结果表明：低熔点琼脂糖包埋法提取的基因组DNA片段明显大于后两种方法，采用0.5％琼脂糖凝胶电泳3h，仍然跑不出加样孔。将该方法提取的基因组DNA稀释100倍作为模板，采用长距离PCR方法，获得了枯草杆菌生物素操纵子基因全长。说明以低熔点琼脂糖包埋法提取枯草杆菌基因组DNA，并获得较大的DNA片段，是完全可行的。
2．枯草杆菌生物素操纵子基因的克隆
将枯草杆菌基因组DNA稀释后，通过PCR反应条件的优化，分别扩增得到了生物素操纵子基因的长距离PCR产物(10.3kb)和3个分段PCR产物。而后采用TA克隆方法，经PCR产物的纯化、两端加A、pGEM-T载体连接、转化大肠杆菌、阳性克隆的酶切鉴定及重组质粒测序，分别获得了生物素操纵子基因3个片段(bio-1、bio-2、bio-3)的克隆质粒。应用分子生物学软件对测序结果进行了分析，并与Genebank中枯草杆菌168菌株的生物素操纵子基因序列进行了对比分析：共有12个碱基差异，且7个碱基导致了氨基酸变异，但未出现移码突变现象。
利用长距离PCR扩增引物为测序引物，利用PCR产物直接测序法，在长距离PCR产物两侧各测了1个反应，并与Genebank中168菌株序列进行了对比分析：两个菌株的序列基本吻合，只有1个碱基的差异。
通过2种方法对3个基因片段的转化效率比较和质粒浓度的测定(重复多次)，
结果表明:biow基因作为大肠杆菌的外源基因，插入高拷贝的pGEM一T载体中，重
组后的质粒具有不稳定性。
3.枯草杆菌部分基因组文库的构建及筛选
首先，通过对枯草杆菌生物素操纵子基因序列和基因组序列的分析，选择刀。脚Hl
和KPnl位点。用这2个内切酶分别将基因组DNA和BluescriPt SKM13载体完全酶
切消化，分别纯化回收(酶切的基因组DNA回收4.3一7kb间的片段)，并用几DNA
Ligase连接，转化大肠杆菌DHS。。
应用PCR快检法对构建的枯草杆菌部分基因组文库进行了筛选，共检测了250
个菌落，得到了3个阳性克隆子，经酶切鉴定和测序，获得了生物素操纵子5.Ikb的
BamHI一KPnl亚克隆片段。测序结果表明:ASI .1 094菌株与168菌株bioAFDB基因
序列完全一致，9个差异碱基是由于PCR扩增导致的。
枯草杆菌生物素操纵子基因4个亚克隆序列的测序结果证实，ASI .1 094菌株和
168菌株生物素操纵子基因序列是完全一致的(见附件1)。
4.枯草杆菌生物素操纵子基因序列的改造
基因序列改造的关键是删除bioB与biof基因间的终止子，在Bowe:等(1 996)
[’97]序列研究分析的基础上，设计一对PcR引物，以bi。一2片段克隆质粒为模板，采
用Skip PCR方法，得到了约4.3kb产物，以TA克隆方式，插入pGEM一T载体中。将
经鉴定的阳性克隆质粒进行测序，结果表明:bioB与biol基因间的5 lbp的终止子序
列已被删除。在基因序列分析的基础上，采用特征酶酶切的方式，还删除了生物素操
纵子基因上、下游与生物合成无关的序列。并将改造后的枯草杆菌生物素操纵子基因
的3个片段依次插入pGEM一T载体中。并经binw、bioB及biol基因3’端的引物进
行PCR扩增和重组质粒酶切鉴定而得到证实。
5.改造后的生物素操纵子基因的功能表达检测及biow和 bioB基因的诱导表达
为了检测改造后的生物素操纵子基因是否能够正常表达，我们利用生物素是细菌
生长的必需物质这一特点，用4种大肠杆菌生物素缺陷株(R874、R875、R877、R879)
经遗传互补分析表明:改造后的生物素操纵子中的bioA、binF、bioD、bioB4个基因
均能够表达。因此，bioB与biof基因间终止子序列的删除，不影响基因的表达。
同时也证实，虽然所克隆的枯草?
It was one of hot spots of high-technologic competition that biotin was produced by using genetically engineered technology. It could improve carcass quality meat quality, reproductive ability of livestock, and was indispensible matter for normal elaboration of livestock's varietal performance.Up till now, biotin could only be gained by the method of chemical synthesis and only imported from the foreign countries,and its price was very expensive and seriously restricted the development of our country's animal husbandry. Alongside rising of genetically engineered technology, the people begined to research biotin biosynthesis. The biosynthetic method could carry on the specific synthesis of biotin and overcome the low yield, nonspecific synthesis and nessary use of the chemical separation for chemically synthetic method.This method could reduce manufacturing cost of biotin, and improved economic benefits of animal husbandry. The use of this method had importantly theoretical meaning and economic value.
Used As 1.1094 strain of Bacillus subtilis as researched material, the structural genes of biotin operon(bio operon) were cloned, and its sequence were engineered. Then the engineered genes of bio operon were carried on testing of the functional expression, and bioW & bioB gene were induced to express. This experiment probed how to improve the expression efficiency of the structural genes of bio operon, and provided the feasibly researched route and scientifically theoretical foundation. For highly efficient expression of the structural genes of bio operon, a lot of researched materials were constructed which could commercially operated in this experiment and these materials provided some explored experience and reference materials for future research. The study mainly carried on several research followed: 1. Extraction of large-fragment genomic DNA
In order to gain DNA template of PCR amplification (Long PCR amplification and salvage PCR amplification) which was high purity and large fragment, three methods were used to extract genomic DNA of Bacillus subtilis, i.e. low melting-point agarose embedding method, SDS-Proteinase K-Phenol Chloroform extraction method and bacterial genomic DNA extraction kit method. The genomic DNA of Bacillus subtilis were gained
by these methods, and the operated programs of the methods were improved. The results showed that the genomic DNA extracted by low melting-point agarose embedding method were obviously biggest than that of another two methods. Used the genomic DNA extracted by low melting-point agarose embedding method as PCR template, the full length of structural genes of Bacillus subtilis bio operon were gained by long PCR method. The results also explained that it was feasible that the genomic DNA of Bacillus subtilis were extracted and gained large DNA fragments by low melting-point agarose embedding method.
2. Cloning of structural genes of Bacillus subtilis bio operon
Diluted the genomic DNA of Bacillus subtilis as the template, long PCR product (10.3kb) and three salvage PCR products were separately gained by optimization of reaction conditions of PCR. Then used TA cloning method, The plasmids of three fragments( bio-1 bio-2 bio-3) of structural genes of Bacillus subtilis bio operon were gained by the purity of PCR products adding A in the two side of the products ligation with pGEM-T vector transformed Escherichia col identification and sequencing of recombinant plasmid. Contrasting analysis with the genes sequence of Bacillus subtilis 168 strain's bio operon, the sequence of bio operon of As 1.1094 strain had 12 bases difference with that of 168 train,and 7 bases caused variation of amino acid.
Used long PCR primers as sequencing primer, the two sides of sequence of the long PCR product were separately sequenced one reaction by the direct sequencing method of PCR products, and the sequencing sequence were carried on constrasted analysis with sequence of 168 strain in Genebank. The results showed that the sequence of two strains basically coincided but
引文
1. Alexeev, D. et al. Sequence and crystallization of Escherichia coli dethiobiotin synthetase, the penultimate enzyme of biotin biosynthesis. J. Mol. Biol. 1994, 235:774-776
2. Allan Campbell et al. Biotin Regulator (bir) Mutations of Escherichia coli. Journal of Bacteriology. 1980,142 (3): 1025-1028.
3. Andrea Pimenta et al. To be free or not: the fate of pimelate in Bacillus sphaericus and in Escherichia coli. Molecular Microbiology. 1995, 19:639-647
4. Andree Marquet et al. Biosynthesis of Biotin and Lipoic Acid. Vitamins and Hormones.2001, 61:51-101
5. Annick Mejean et al. Highly Purified Biotin Synthase Can Transform Dethiobiotin into Biotin in the Absence of Any Other Protein, in the Presence of Photoreduced Deazaflavin. Biochemical and Biophysical Research Communications. 1995, 217 (3) :1231-1237
6. Anthony J et al. The Escherichia coli Biotin Biosynthetic Enzyme Sequence Predicted from the Nucleotide Sequence of the bio operon. The Journal of Biological Chemistry.1988,263(36):19577-19585
7. Anthony Otsuka, John Abelson et al. The regulator region of the biotin operon in Escherichia coli. Nature. 1978.276:689-694
8. Ayumi Fujisawa et al. Biotin Production by bioB Transformants of a Bacillus sphaericus Mutant Resistant to 1-(2'-Thenoyl)-3, 3, 3-trifluoroacetone, an Electron Transport Inhibitor. Biosci. Biotech. Biochem. 1994.58(6): 1018-1022
9. Azevedo, V. et al. The transcriptional organization of the Bacillus subtilis 168 Mol.Microbiol. 1993, 10:397-405
10. Barbara Hartl et al. Development of a New Integration Site within the Bacillus subtilis Chromosome and Construction of Compatible Expression Cassettes. Journal of Bacteriology. 2001, 183 (8):2696-2699
11. Barnes WM. PCR amplification of up to 35 kb with high fidelity and high yield form λ bacteriophage templates. Proc Natl Acad Sci USA, 1994, 91:2216-2220
12. Bartra Sk. et al. A simple, effective method for the construction of subtracted cDNA libraries. Gene Anul Technol. 1991, 8:129-133
13. Batzer MA. et al. Enhanced evolutionary PCR using oligonucleotides with inosine at the 3'-terminus. Nucleic Acids Res, 1991, 91:5081
14. Bell DA, Demarini D. Excessive cycling converts PCR products to random-length higher molecular weight fragments. Nucleic Acids Res, 1991, 91:5079
15. Bhat GJ et al. A simple method for cloning blunt ended DNA fragments. Nucleic Acids Res, 1991, 19:398
16. Birch, O. M. et al. Biotin synthase from Escherichia coli, an investigation of the low molecular weight and protein components required for activity in vitro. J. Biol. Chem. 1995, 270:19158-19165
17. Blumberg DD. Creating a ribonuclease free environment, Methods Enzvmol, 1987, 152: 20-24
18. Bokhee Kim et al. Adapting homogeneous enzyme-linked competitive binding assays to microtiter plates. Analytical Biochemistry. 1994, 218:14-19
19. Bower, S. et al. Biotin biosynthesis in Bacillus subtilis. European patent application 1994, 94108998.9
20. Brown, T. A., ed. Molecular Biology Labfax. BIOS Scientific Publishers. Oxford, 1991
21. Burke, D. T. et al. Cloning of large segments of exogenous DNA into yeast by means of artificial chromosome vectors. Science, 1987.236:806-812
22. Calvin, N. M. and Hanawalt P. C. High efficiency transformation of bacterial cells by electroporation. J. Bacteriol. 1988.170:2796-2801
23. Cha J. et al. New vectors for direct cloning of PCR products, of 1993, 136:369-370
24. Cheng S, Chang SY, Gravitt P, Respess R. Long PCR. Nature, 1994, 369:684-685
25. Cheng S, Fockler C, Barnes WM et al. Effective amplification of long targets from cloned inserts and human genomic DNA. Proc Natl Acad Sci USA, 1994, 91:5695-5699
26. Cheng S, Higuchi R, Stoneking M. Complete mitochondrial genome amplification.Nature Genet, 1994, 7:350-351
27. Cheng S. et al. Template integrity is essential for PCR amplification of 20-to 30-kb sequences from genomic DNA. PCR Meth Appl, 1995, 4:294-298
28. Cheng S. Longer PCR amplifications in eds. Innis MA, Gelf and DH, Sninsky JJ. PCR Strategies, San Diego, CA: Academic, 1995:313-324
29. Chou Q. et al. Prevention of pre-PCR mis-priming and primer dimerization improves low copy number amplifications. Nucleic Acids Res, 1992, 20:1717-1723
30. Church DM. et al. Isolation of genes from complex sources of mammalian genomic DNA using exon amplification. Nature Genet. 1994, 6: 98-105
31. Chwen-Huey Wu et al. Isolation and characterization of the Erwinia herbicola bio operon and the sequences of the bioA and bioB genes. Gene. 1996, 174:251-258
32. Chwen-Huey Wu et al. Molecular Cloning and Nucleotide Sequencing of BioF (7-Keto-8-Amino Pelargonic Acid Synthetase), BioC and BioD (Dethiobiotin Synthetase) Genes of Erwinia Herbicola. Biochemistry and Molecular Biology International. 1997, 41 (2):311-315
33. Clark JM. Novel non-template nucleotide addition reactions catalysed by procaryotic and eucaryotic and eucaryotic DNA polymerase. Nucleic Acids Res. 1988, 20:9677-9686
34. Costa GL, Weiner Mp. Protocols for cloning and analysis of blunt-ended PCR-generated DNA fragments. PCR Meth Appl, 1994, 3: S95-S106
35. D, Souza CR et al. A simplifed procedure for cDNA and genomic library construction using nonpalindromic oligonucleotide adaptors. Biochem cell Biol. 1989.67:205-209
36. D. Speck et al. Isolation of Bacillus sphaericus biotih synthesis control mutants: evidence for transcriptional regulation of bio genes. Gene. 1991, 108: 39-45
37. D' Aquila RT et al. Maximizing sensitivity and specificity of PCR by preamplification heating. Nucleic Acids Res. 1991.19:37-49
38. David A. Patton et al. An Embryo-Defective Mutant of Arabidopsis Disrupted in the Final Step of Biotin synthesis. Plant Physiol. 1998, 116:935-946
39. David A. Patton et al. Complementation of an Arabidopsis thaliana biotin auxotroph with an Escherichia coli biotin biosynthetic gene. Mol Gen Genet. 1996, 251: 261-266
40. David F. Barker et al. Sequence and properties of operator mutations in the bio operon of Escherichia coli. Gene. 1981, 13:89-102
41. David F. Barker et al. Use of bio-lac Fusion Strains to Study Regulation of Biotin Biosynthesis in Escherichia coli. Journal of Bacteriology. 1980, 143(2): 789-800
42. David Shiuan et al. Transptional analysis of the Escherichia coli bio operon. Gene.1994, 145: 1-7
43. David Shiuan, Allan Campbell. Transcriptional regulation and gene arrangement of Escherichia coli, citrobacter freundii and Salmonella typhimurium biotin operons.Gene. 1988, (67) :203-211
44. Davis LG. et al.Basic Methods in Molecular Biology. New York: Elsevier, 1986
45. De Leenheer AP et al. Modern chromatographics analysis of the vitamins, New York: Marcol Dekoker, 1985:447
46. Delidow BC. Molecular Cloning of polymerase chain reaction fragments with cohesive ends, in ed. White BA. PCR Protocols: Current Methods and Applications. Totowa, NJ. Humana, 1993:217-228
47. Denman, J., M. Hayes and C. O. Day, et al. 1991. Transgenic expression of a variant of
human tissue-type plasminogen activator in goat milk: purification and characterization of the recombinant enzyme. Biotechnology,9:839～843
48. Dmitry A. Rodionov et al. Conservation of the biotin Regulation and the BirA Regulatory signal in Eubacteria and Archaea. Genome Research. 2002, 12:1507-1516
49. Dominique Florentin et al. On the mechanism of biotin synthase of Bacillus sphaericus. C. R. Acad. Sci Paris, Science de la vie/life sciences. 1994, 317:485-488
50. Don RH. et al. 'Touchdown' PCR to circument spurious priming during gene amplification. Nucleic Acids Res, 1991, 19:4008
51. Donald M. Mock et al. A Fluorometric Assay for the biotin-Avidin Interaction Based on Displacement of the Fluorescent Probe 2-Anilinonaphthalene-6-sulfonic Acid. Analytical Biochemistry. 1985.151: 178-181
52. Dorothy Beckett. [21] Energetic Methods to study Bifuctional Biotin Operon Repressor.Methods in Enzymology. 1998, 295:424-451
53. Dower, W. J. et al. High efficiency transformation of E. coli by high voltage electroporation. Nucl. Acids. Res. 1988.16:6127-6145
54. Dycaico M et al. Reduce PCR false positives using the Stratalinker UV crosslinker. Stratagene Strategies, 1991, 4(3): 39-40
55. E. Joan William and Anthony K. Campbell. A Homogeneous Assay for bioth Based on chemiluminescence Energy Transfer. Analytical Biochemistry. 1986. 155:249-255
56. Ebert, K. M., M. J. Low and E. W. Overstrom et al. 1988. A moloney MLV-rat somatotropin fusion gene produces biologically active domatotropin in a transgenic pig. Mol. Endocrin, 2:277～283
57. Edward A. Bayer et al. A Sensitive Enzyme Assay for Biotin, Avidin, and Streptavidin.Analytical Biochemistry. 1986. 154:367-370
58. Edward Demol and William Shive. Assay for Biotin in the presence of Dethiobiotin with Lactocacillus Plantarum. Analytical Biochemistry. 1986. 158:55-58
59. Edward Eisenstein et al. Dimerization of the Escherichia coli biotin repressor:corepressor function in protein assembly. Biochemistry, 1999, 38:13777-13804
60. Eisenbery, M. A. Biosynthesis of biotin and lipoic acid, P.554-560.In F. C. Neidhardt. J. L. Ingraham, B. et al. Escherichia coli and Salmonella typhimurium: cellual and molecular biology. American Society for Microbiology, Washington, D. C.
61. Elizabeth H. et al. A physical map of the Escherichia coli bio operon. Gene. 1982.19:93-103
62. Emily D. Streaker, Dorothy Beckett. Coupling of Site-Specific DNA Binding to Protein Dimerization in Assembly of the Biotin Repressor-Biotin Operator Complex.
Biochemistry. 1998, 37, 3210-3219
63. Erlich HA et al. Recent advances in the ploymerase chain reaction, Science. 1991, 252:1643-1651
64. Errington, J. Efficient Bacillus subtilis cloning system using bacteriophage vector φ 10591. Journal of General Microbiology, 1984, 130:2615-2628
65. Evangelia Livaniou et al. Analytical techniques for determining biotin. Journal of Chromatography A. 2000, 881:331-343
66. F. kunst et al. The complete genome sequence of the Gram-positive bacterium Bacillus subtilis. Nature. 1997. 390:249-256
67. Florentin, D. et al. On the mechanism of biotin synthetase of Bacillus Spaericus. C. R. Acad. Sci. Ser. III 317:485-488
68. Forrester HB. et al. Amplification of Low copy number, large DNA sequences in human genomic DNA using Tub DNA polymerase. Biotechniques, 1994, 17:20-22
69. Friedmann KD. et al. Enzymatic amplification of specific cDNA inserts from λ gt11 libraries.Nucleic Acids Res. 1988.16: 8718
70. FrischaufAM. Construction and characterization ofa genomic library in λ. Methods Enzyzmol,1987, 152:190-199
71. Gary Ketner, Allan Campbell et al. Operator and Promoter Mutations Affecting Divergent Transcription in the bio Gene Cluster of Escherichia coli. J. Mol. Biol. 1975,96:13-27
72. Gibson. K. J. et al. Dethiobiotin Synthetase: the carbonylation of 7, 8-diaminononanoic acid proceeds regiospecifically via the N7-carbamate. Biochemistry. 1995, 34: 10976-10984
73. Gossler, A.and R. Ralling. 1992. The molecular and genetic analysis of mouse development. Eur. J. Biochem., 204:5～11 Grosveld, E. and G. Kollias. 1992. Transgenic animals. Academic Press
74. Grazyna Konopa et al. A physical map of the bioAB region in the λ bio transducing phage. Gene. 1982. 19:104-108
75. Gunter Schneider, Ylva Lindqvist. Structural enzymology of biotin biosynthesis. FEBS Letters. 2001, 495:7-11
76. Gussow D, Clackson T. Direct clone characterization from plaques and colonies by the polymerase chain reaction. Nucleic Acids Res, 1989, 17:4000
77. Hammer, R.E., V. G. Pursel and C. E. Rexroad et al. 1985. Production of transgenic rabbits, sheep and pigs by microinjection. Nature, 315:680～683
78. Hanahan D. Studies on transformation of E. coli with plasmids. J Mol Biol. 1983. 166:
557-580
79. Harrison J et al. Direct cloning of polymerase chain reaction products in an XcmI T-vecter. Anal Biochem, 1994, 216:235-236
80. Hartmut R. Schroeder et al. Competitive protein binding assay for biotin monitored by chemiluminescence. Analytical Chemistry. 1976, 48 (13): 1933-1937
81. Harwood, C. R. et al. Growth, maintenance and general techniques, P. 7. In C. R. Harwood and S. M. Cutting (ed.), Molecular biological methods for Bacillus. John Wiley & Sons, Chichester, England 1990.
82. Haymerle H et al. Efficient construction of cDNA libraries in plasmid expression vectors using an adapter strategy. Nucleic Acids Res. 1986, 14:8615-8624
83. Hecker KH, Roux KH. High and low annealing temperatures increase both specificity and yield in TD and SD PCR. Biotechniques, 1996, 20:478-485
84. Heery DM et al. A simple method for subcloning DNA fragments from gel slices. Trends Genet. 1990, 6:173
85. Hideaki Yamada et al. Biotin Overproduction by Bioth Analog-resistant Mutants of Bacillus sphaericus. Agric. Biol. Chem. 1983, 47(5): 1011-1016
86. Holland PM et al. Detection of specific polymerase chain reaction product by utilizing the 5'-3' exonuclease activity of Thermus aquaticus DNA polymerase. Proc Natl Acad Sci USA, 1991, 88:7276-7280
87. Holton TA, Graham MW.A simple and efficient method for direct cloning of PCR products using ddT-tailed vectors. Nucleic Acids Res, 1991, 19:1156
88. Horton RM, Hoppe BL, Conti-Tronconi BM. AmpliGrease, "Hot Start" PCR using petroleum jelly. Biotechniques, 1994, 16:42-43
89. Hu G. DNA polymerase-catalyzed addition of nontemplated extra nucleotides to the 3' end of a DNA Fragmet. DNA cell Biol, 1993, 12:763-770
90. Huang SH, et al. Amplification of gene ends from gene libraries by PCR with single-sided specificity. Methods Mol Biol. 1993, 15:357-363
91. Huang W. et al. Mechanism of an ATP-dependent carboxylase, dethiobiotin synthetase, based on crystallographic studies of complexes with substrates and a reaction intermediate. Biochemistry. 1995, 34:10985-10995
92. Hueck, C. J., W. Hillen. Catabolite repression in Bacillus subtilis: a global regulatory mechanism for the gram-positive bateria? Mol. Microbiol. 1995, 15:395-401
93. I chihara Y, kurosawa Y. Construction of new T vectors for direst cloning of PCR products. Gene, 1993, 130:153-154
94. I ohsawa et al. Cloning of the biotin synthetase gene from Bacillus sphaericus and
expression in Escherichia coli and Bacilli. Gene, 1989, (80): 39-48
95. Ifuku O. et al. Flavodovin is required for conversion of dethiobiotin to biotin in Escherichia coli. Eur. J. Biochem. 1994, 224:173-178
96. Ifuku, O. et al. Conversion of dethiobiotin to biotin in cell-free extracts of Escherichia coli. Bioci. Biotechnol. Biochem. 1992, 56:1780-1785
97. Ilya G. Serebriiskii et al. Two new members of the BioB superfamily: cloning, Sequencing and expression of bioB genes of Methylobacillus fiagellatum and Corynebacterium glutamicum. Gene. 1996, 175: 15-22
98. Indrajit Sanyal et al. Escherichia coli Biotin Synthase: An Investigation into the Factors Required for Its Activity and Its Sulful Donor. Archives of Biochemistry and Biophysics. 1996. 326(1): 48-56
99. Inoue, H. et al. High efficiency transformation of Echerichia coli with plasmids. Gene.1990, 96:23-28
100. Isola NR. et al. Screening recombinant DNA libraries: a rapid and efficient method for isolating cDNA clones utilizing the PCR. BioTechniques. 1991.11:580-582
101. Iwahana H et al. T-cassette ligation: a method for direct sequencing and cloning of PCR-amplified DNA fragments. PCR Methods Applic. 1994, 3:219-224
102. Jeanette E Stok, James J. De Voss. Expression, Purification, characterization of BioI: A Carbon-Carbon Bond Cleaving Cytochrome P450 involved in Biotin Biosynthesis in Bacillus subtilis. Archives of Biochemistry and Biophysics. 2000, 384(2): 351-360
103. Jennifer Abbott, Dorothy Beckett. Cooperative Binding of the Escherichia coli Repressor of Biotin Biosynthesis to the Biotin Operon Sequence. Biochemistry. 1993, 32, 9649-9656
104. Jepson I et al. A rapid procedure for the construction of PCR cDNA libraries from small amounts of plant tissue. Plant Mol Biol Reporter. 1991, 9:131-138
105. Jeroo Kotval et al. Leftward transcription in the Escherichia coli bio operon does not require products of the right word transcript. Gene. 1982, 17:219-222
106. John B. Perkins et al. Indentification and characterization of transcriptions from the biotin biosynthetic operon of Bacillus subtilis.Journal of Bacteriology. 1996.178(21);6361-6365
107. John E. cronan, Jr. Expression of the biotin Biosynthetic Operon of Escherichia coli Is Regulated by the Rate of Protein Biotination. The Journal of Biological Chemistry.1988, 263(21):10332-10336
108. John E. Cronan, Jr., The E. coli bio operon: Transptional Repression by an Essential Protein Modification Enzyme. Cell 1989, 58:427-429
109. John T. Sullival et al. The bio operon on the acquired symbiosis island of Mesorhizobium sp. Strain R7A includes a novel gene involved in pimeloyl-coA synthesis. Microbiology, 2001, 147:1315-1322
110. John T. Sullivan et al. The bio operon on the acquired symbiosis island of Mesorhizobium Sp. Strain RTA includes a novel gene involved in pimeloyl-CoA synthesis. Microbiology. 2001, 147:1315-1322
111. Kaiser, K. and Murray, N. E. The use of phage lambda replacement vectors in the construction of representative genomic DNA libraries. In DNA cloning: A practical Approach, vol. 1 (D.M. Glover, ed. )PP. 1-47. IRL Press, Oxford. 1984
112. Kaith J. Schray and Pamela G. Artz. Determination of Avidin and Biotin by Fluorescence Polarization. Anal. Chem. 1988, 60:853-855
113. Kaufman DL, Evans GA. Restriction endonuclease cleavage at the termini of PCR products. Biotechniques, 1990, 9:305-306
114. Keehwan Kwon et al. Multiple disordered loops function in corepressor-induced dimerization of the biotin repressor. J. Mol. Biol. 2000, 304:821-833
115. Keith P. Wilson et al. Escherichia coli biotin holoenzyme synthetase/bio repressor crystal structure delineates the biotin- and DNA-binding domains. Proc. Natl. Acad. Sci. USA. 1992, 89:9257-9261
116. Kevin M. Vchida, Anthony J. Otsuka. Isolation and characterization of Escherichia coli birA intragenic suppressors. Mol Gen Genet 1987, 210:234-240
117. Kinttel T, Picard D. PCR with degenerate primers containing deoxyinosine fails with pfu DNA polymerase. PCR Meth Applic, 1993, 2:346-347
118. Kogl F. Uber Wuchsstoffe der Auxin-under Biosgurppe. Ber, 1935, 68A: 16(CA,1935, 29: 2563)
119. Kolmodin L et al. GeneAmp XL PCR kit. Amplification: A Forum for PCR users (The Perkin-Elmer coporation), 1995, 13:1-5
120. Kovalic D et al. General method for direct cloning of DNA fragments generated by the polymerase chain reaction. Nucleic Acids Res, 1991, 19:4560
121. Kripamoy A et al. An improved method for the construction of high efficiency cDNA library in plasmid or lambda vector Nucleic Acids Res. 1990, 18:1071
122. Kuo-Chih Lin et al. Binding characteristics of Escherichia coli biotin repressor-operator complex. Biochimica et Biophysica Acta. 1991, 1090:317-325
123. Kwok S, Higuchi R. Avoiding false positives with PCR. Nature. 1989. 339:237-238
124. Lardelli M, lendahl U. Generating bacteriophge λ sublibraries enriched for rare clones. BioTechniques. 1994, 16:420-422
125. Larry H. Weaver et al. Corepressor-induced organization and assembly of the biotin repressor: A model for allosteric activation of a transcriptional regulator. Proc. Natl. Acad. Sci. USA, 2001, 98(11): 6045-6050
126. Lau EC et al. Preparation of denatured plasmid templates for PCR amplification.Biotechniques. 1993, 14:378
127. Lauer, G. et al. Cloning, nucleotide sequence, and engineered expression of Thermus thermophilus DNA ligase, a homolog of Ecsherichia coli DNA ligase. J. Bacteriol. 1991, 173:5047-5053
128. Lemoine, Y. et al. To be free or not: the fate of pimelate in Bacillus sphaericus and in Escherichai coli. Mol. Microbiol. 1996. 19:645-647
129. Lerner, C. G., M. Inonye. Low copy number plasmids for regulated Low-lever expression of cloned genes in Escherichia coli with blue/white insert screening capability. Nucleic Acids Res. 1990. 18:4631
130. Lisa M. Weaver et al. Characterization of the cDNA and Gene Coding for the Biotin Synthase of Arabidopsis thaliana. Plant Physiol. 1996, 110:1021-1028
131. Lisa McIver et al. Indentification of the [Fe-s] cluster-binding residues of Escherichia coli biotin synthase.The Journal of Biological Chemistry, 2000, 275(18): 13888-13894
132. Luo MZ, Cella R. A reliable amplification technique with single-sided specificity for the isolation of 5'gene regulating region. Gene. 1994, 140:59-62
133. Lynn Farh et al. Structure-Fuction Studies of Escherichia coli Biotin Approach. J. Biochem. 2001, 130:627-635
134. M. Friggs et al. Biotin inclusion helps optimize animal performance. Feedstuffs. 1994, (1): 12-13
135. Maloy, S. R. Experimental techniques in bacterial genetics, P.48. Jones and Bartlett Publishers, Boston. 1990.
136. Marchuk D. et al. Construction of T-vectors, a rapid and general system for direct cloning of unmodified PCR products. Nucleic Acids Res, 1991, 19:1154
137. Martin R. Buoncristaini, Anthony J. Otsuka. Overproduction and Rapid purification of the Biotin Operon Repressor from Escherichia coli. The Journal of Biologcal Chemistry. 1988, 263(2): 1013-1016
138. Martin R. Buoncristiani et al. DNA-binding and enzymatic domains of the bifunctional biotin operon repressor (BirA) of Escherichia coli. Gene. 1986, 44:255-261
139. Max A. Eisenbery et al. Mode of Action of the Biotin Antimetabolites Actithiazic
Acid and α-Methyldethiobiotin. Antimicrobial Agents and chemotheraphy. 1982,21(1):5-10
140. Mead DA et al. A universal method for the direct cloning of PCR amplified nucleic acid. Bio/Technology, 1991, 9:657
141. Meissner PS et al. Bacteriophage lambda cloning system for the construction of directional cDNA libraries. Proc Natl Acad Sci USA, 1987, 84:4171-4175
142. Messing J. New M13 vectors for cloning. Methods Enzymol. 1983, 101:20-78
143. Michael Young et al. Gene Amplification in Bacillus subtilis. Journal of General Microbiology. 1984, 130:1613-1621
144. Monforte JA et al. Megabase genomic DNA isolation procedure for use in transgenic mutagenesis assays. Environ Mol Mutagenesis 1994, 23:46
145. Mullis KB et al. eds. The polymerase Chain Reaction. Boston, MA: Birkhauser, 1994
146. Mullis KB, Erlich HA. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988, 239:487-491
147. Munroe DJ et al. Systematic screening of an arrayed cDNA library by PCR. Proc Natl Acad Sci USA. 1995.92:2209-2213
148. N M Shaw et al. Biotin production under limiting growth conditions by Agrobacterium/Rhizobium HK4 transformed with a modified Escherichia coli bio operon. Journal of Industrial Microbiology & Biotechnology. 1999, 22:590-599
149. Naoki Sakurai et al. Complete Sequence and organization of the serratia marcescens biotin operon. Microbiology, 1996, 142: 3295-3303
150. Naoki Sakurai et al. Construction of a Biotin-Overproducing Strain of Serratia marcescens. Applied and Environmental Microbiology. 1993, 59 (9) :2857-2863
151. Naoki Sakurai et al. Instability of the mutated biotin operon plasmid in a biotin-producing mutant of Serratia marcescens, Journal of Biotechnology. 1995 (43) :11-19
152. Naoki Sakurai et al. Molecular Breeding of a Biotin-Hyper producing Serratia marcescens Strain.Applied and Environmental Microbiology. 1993, 59 (10):3225-32312
153. Naotake Ogasawara. Systematic function analysis of Bacillus subtilis genes. Res. Microbiol. 2000, 151: 129-134
154. Natalia B. et al. Biotin Synthase Contains Two Distinct Iron-Sulfur Cluster Binding Sites: Chemical and Spectroelectrochemical Analysis of Iron-Sulfur Cluster Interconversions. Biochemistry. 2001, 40:8343-8351
155. Nicholas H. Tomczyk et al. Purification and characterization of the BIOH proteim
from the biotin biosynthetic pathway. FEBS letters. 2002, 513:299-304
156. Nicholas M. Shaw et al. Biotin synthase from Escherichia coli: isolation of an enzyme-generated intermediate and stoichiometry of s-adenosylmethionine use. Biochem J. 1998.330:1079-1085
157. Nickloff, J. A. and Reynolds, R. J. Subcloning with new ampicillin and kanamycin resistant analogs of pUC19. Biotechniques. 1991.10:469-472
158. Nyles W. Charon et al. Isolation of Lambda Transducing Phage with the bio Genes Inserted Between Lambda Genes P and Q. Genetics. 1980, 95: 1-13
159. Ohji Ifuku et al. Molecular Analysis of Growth Inhibition Caused by Overexpression of the Biotin Operon in Escherichia coli. Bioci. Biotech. Biochem. 1995, 59(2):184-189
160. Ohji Ifuku et al. Origin of carbon atoms of biotin ~(13)C-NMR studies on biotin biosynthesis in Escherichia coli. Eur. J. Biochem. 1994, 220:585-591
161. Ohji Ifuku et al. Sequencing Analysis of Mutation Points in the Biotin Operon of Biotin-overproducing Escherichia coli Mutants. Biosci. Biotech. Biochem. 1993, 57 (5) :760-765
162. Olivier ploux et al. Mechanistic studies on the 8-amino-7-oxopelargonate synthase, a pyridoxal-5'-phosphate-dependent enzyme involved in biotin biosynthesis. Eur. J. Biochem. 1996. 236:301-308
163. OM Prakash, Max A. Eisenberg. In vitro synthesis and Regulation of the Biotin Enzymes of Escherichia coli K- 12. Journal of Bacteriology. 1978, 134 (3): 1002-1012
164. Palmer, M.S., A. H. Sinclair and P. Berta et al. 1989. Genetic evidence that ZFY is not the testis determing factor. Nature, 342:937～939
165. Palva, I. Molecular cloning of α-amylase gene form Bacillus amyloliquefaciens and its expression in B. subtilis. Gene, 1982, 19:81-87
166. Parimoo S et al. cDNA selection: efficient PCR approach for the selection of cDNAs encoded in large chromosomal DNA fragments. Proc Natl Acad Sci USA. 1991.88: 9623-9627
167. Patanjali SR et al. Construction of a uniform-abundance (normalised) cDNA library. Proc Natl Acad Sci USA. 1991. 88:1943-1947
168. Patil RV, Dekker EE. PCR amplification of an Escherichia coli positions in degenerate amino acid codons. Nucleic Acids Res, 1990, 18:3080
169. Paul A. Smith et al. A plasmid expression system for quantitative in vivo biotinylation of thioredoxin fusion protein in Escherichia coli. Nucl. Acids. Res. 1998, 26(6):1414-1420
170. Perkins, J. B. and J. G. Pero. Biosynthesis of riboflavin, biotin, folic acid, and Cobalamin, P. 319-334. In A. L. Sonenshein, J. A. Hoch, and R. losick (ed.). Bacillus subtilis and other gram-positive bacteria: biochemistry, physiology, and molecular genetics. American Society for Microbiology, Washington, D. C.
171. Peter K. Howard et al. Nucleotide sequence of the birA gene synthetase functions of Escherichia coli. Gene. 1985, 35:321-331
172. Pierce JC et al. A positive selection vector for cloning high molecular weight DNA by the bacteriophage P1 system: improved cloning efficacy. Proc Natl Acad Sci USA. 1992.89-2056-2060
173. Pierre Baldet et al. Biotin synthesis in higher plant: Purification and charaterization of bioB gene product equivalent from Arabidopsis thaliana overexpressed in Escherichia coli and its subcellular localization in Pea leaf cells. FEB S letter. 1997.419:206-210
174. Plamena Entcheva et al. Fuctional Analysis of Sinorhizobium Meliloti Genes Involved in Biotin Synthesis and Transport. Applied and Environmental Microbiology.2002, 68(6): 2843-2848
175. Ploux, O. et al. Investigations of the first step of biotin biosynthesis in Bacillus sphaericus. Purfication and characterization of the pimeloyl-CoA Synthetase and uptake of pimelate. Biochem. J. 1992.287:685-690
176. Ploux, O. et al. The 8-amino-7-oxoate pelargon synthase from Bacillus sphaericus. Pruification and preliminary characterization of the cloned enzyme overproduced in Escherichia coli. Biochem J. 1992, 283: 321-327
177. Pouwels, P. H. et al. Cloning Vectors: A Laboratory manual. Elsevier Science Publishing, Amsterdam, 1985
178. R. Alonso et al. Rapid extraction of high purity chromosomal DNA form serratia marcescens. Letters in Applied Microbiology. 1993.16:77-79
179. R. Gleockler et al. Cloning and characterization of the Bacillus spaericus genes controlling the bioconversion of pimelate into dethiobiotin. Gene. 1990, 87:63-70
180. Ralph W. et al, Bacteriocins of Gram-Positive Bacteria Microbiological Reviews. 1995, 59(2): 171-200
181. Richard G. Brennan et al. Crystallization of the Bifunctional Biotion operon Repressor. The Journal of Biological Chemistry. 1989, 264 (1) :5
182. Roux KH. Optimization and troubleshooting in PCR. PCR Meth Applic, 1995, 4:S185-S194
183. Rychlik W. New algorithm for determining primer efficiency in PCR and sequencing. J NIH Res, 1994, 6:78
184. Rychlik W. Selection of primers for polymerase chain reaction. In ed. White BA, PCR Protocols: A Guide to Methods and Applications. in methods in Molecular Biology.Vol. 15, NJ:Humana, Totowa, 1993:31-40
185. S. A. Halvatzis and Timotheou-potamia. Kinetic-potentiometric determination of ascorbic acid, biotin, pyridoxine hydrochloride and thiamine hydrochloride with N-bromosuccinimide. Analytical Chimica Acta. 1989, 227:405-499
186. S. A. Yankofsky et al. Solid-Phase Assay for d-Biotin on Avidin-cellulose Disks. Analytical Biochemistry. 1981, 118:307-314
187. S. W. Brown et al. The production of Biotin by Recombinant strains of Escherichia coli. J. Chem. Tech. Biotechnol. 1991, 50:115-121
188. Sambrook J. et al. Molecular cloning: A Laboratory Manual, 2nd eds. Cold Spring Harbour, NY: Cold Spring Harbor Laboratory, 1989
189. Sandhu GS et al. Rapid one-step characterization of recombinant vectors by direct analysis of transformed Escherichia coli colonies. BioTechniques. 1989.7:689-690
190. Sanyal I. et al. Biosynthesis of pimeloyl-CoA, a biotin precursor in Escherichia coli, follows a modified fatty acid synthesis pathway: ~(13)C-labeling studies. J. Am. Chem.Soc. 1994, 116:2637-2638
191. Sanyal I. et al. Biotin synthase: purification, characterization as a [2Fe-2S] cluster protein, and in vitro activity of the Escherichia coli bioB gene product. Biochemistry. 1995, 33:3625-3631
192. Sanyal I. et al. Escherichia coli biotin synthase: an investigation into the factors required for its activity and its sulfur donor. Arch. Biochem. Biophys. 1996, 326: 48-56
193. Scharf SJ. et al. Direct cloning and sequence analyses of enzymatically amplified genomic sequences. Science, 1986, 233:1076-1078
194. Shuguang Zhang et al. The Gene for Biotin Synthase from Saccharomyces cerevisiae: Cloning, Sequencing, and Complementation of Escherichia coli Strains Lacking Biotin Synthase. Archives of Biochemistry and Biophysics. 1994. 309 (1) :29-35
195. Shyamala U, Ames GFL. Genome walking by single-specific primer polymerase chain reaction: ssp-PCR. Gene. 1989, 84:1-8
196. Stanley Bower et al. Cloning and Characterization of Bacillus subtilis birA gene Encoding a Repressor of the Biotin operon. Journal of Bacteriology. 1995, 177 (19) :2572-2575
197. Stanley Bower et al. Cloning, Sequencing and Characterization of the Bacillus subtilis Biotin Biosynthetic Operon. Journal of Bacteriology, 1996, 178 (14): 4122-4130
198. Stephen W. Brown, K. Kamogawa. The Production of Biotin by Genetically Modified Micro-organisms. Biotechnology and Genetic Engineering Reviews. 1991, 9:295-326
199. Steven W. Polyak et al. Biotin Protein Ligase from Saccharomyces Cerevisiae The N-Terminal Domain is Required for Complete Activity. J Biol Chem. 1999, 274: 32847-32854
200. Stewart ACM et al. Generation of entire human papilloma virus genomes by long PCR: frequency of errors produced during amplification. Genome Res, 1995, 5:79-88
201. Stoker AW. Cloning of PCR products after defined cohesive termini are created with T_4 DNA polymerase. Nucleic Acids Res. 1990. 18:4290
202. Struhl K. Arapid method for creating recombinant DNA molecules. BioTechniques.1985.3:452-453
203. Suggs SV et al. Use of synthetic oligodeoxyribonucleotides for the isolation of specific cloned DNA sequences. In eds. Brown DD. Fox GF, Developmental Biology Using Purified Genes. New York: Academic. 1983:683-693
204. Swanson, M.E., M. J. Martin and J.K. O'Donnell et al. 1992. Production of functional human hemoglobin in transgenic swine. Biotechnology, 10:557-559
205. Swapan K. Nath, Arabinda Guha. Abortive termination of bioBFCD RNA synthesized in vitro from the bioABFCD operon of Escherichia coli K-12. Proc. Natl. Acad. Sci. USA. 1982, 79:1786-1790
206. Swapan K. Nath. Attenuation of transption of biotin genes in Escherichia coli. Can. J. Microbiol. 1988, 34:1288-1296
207. Sylvia Daunert et al. Pyruvate carboxylase as a Model for oligosubstituted emzyme-ligand conjugate in homogeneous emzyme immunoassays. Anal. Chem.1989, 61:2160-2164
208. Takashi Ohshiro et al. Enzymatic Conversion of Dethiobiotin to Biotin in cell-free Extracts of a Bacillus sphaericus bioB Transformant. Biosci. Biotech. Biocheml. 1994, 58(9): 1738-1741
209. Takumi T, Lodish HF. Rapid cDNA cloning by PCR screening. BioTechniques. 1994.17:443-444
210. Tatsuya Kiyasu et al. Cloning and characterization biotin biosynthetic genes of kurthia sp. Gene. 2001, (265): 103-113
211. Tatsuya kiyasu et al. Contribution of Cysteine Desulfurase (Nifs Protein) to the Biotin Synthase Reaction of Escherichia coli. Journal of Bacteriology, 2000, 182 (10):2879-2885
212. Testori A et al. Driect cloning of unmodified PCR products by exploiting an
engineered restriction site. Gene, 1994, 143: 151-152
213. Triglia T et al. A procedure for in vitro amplification of DNA segments that lie outside the boundaries of known sequences. Nucleic Acids Res. 1988.16:8186
214. Troutt AB et al. Ligation-anchored PCR: a simple amplification technique with single-sided specificity. Proc Natl Acad Sci USA. 1992.89:9823-9825
215. Tsuguchika Yoshida et al. Liquid chromatographic determination of biotin by using 1-phrenyldlazomethane as a pre-column fluorescent labeling reagent. Journal of chromatography. 1988.456:421-426
216. Unrau P, Deugau KV. Non-cloning amplification of specific DNA fragments from whole genomic DNA digests using DNA "indexers" . Gene. 1994, 145:163-169
217. Uskokovic M R. Kirk-Othmer Encycl Chem Technology [M]. New York: John Wiley & Sons, 1984. 41-49
218. Wada K-N et al. Codon usage tabulated from the GenBank genetic sequence data. Nucleic Acids Res. 1990. 18:2367-2411
219. Wang K et al. A simple method using T_4 DNA polymerase to clone polymerase chain reaction products. BioTechniques, 1994, 17:236-238
220. Weickert, M. J. et al. Site-directed mutagenesis of catabolite repression operator sequence in Bacillus subtilis. Proc. Natl. Acad. Sci. USA. 1990, 87:6238-6242
221. Wendland J A, Lengeler K B, Kothe E. An instant preparation method for nucleic acids of filamentous fungi [J]. Fungal Genetics Newsletter, 1996, 43:54-55
222. White BA. (ed.) Methods in Molecular Biology. Vol. 15. PCR Protocols: Current Methods and Application. Totowa, NJ: Humana, 1993
223. Witkowski JA. 50 years on Molecular Biology Hall of fame. Trends Biotechnol. 1988. 6:234
224. Wolgemuth, D.J., R. R. Behringer and M. P. Mostoller et al. 1989. Transgenic mice overexpressing the mouse hemeo-box containing gene Hox-1.4 exhibit abnormal gut development. Nature, 337:464～467
225. Wu DY. et al. The effect of temperature and oligonucleotide primer length on the specificity and efficiency of amplification by the polymerase reaction. DNA Cell Biol,1991, 10:233-238
226. Yan Xu, Dorothy Beckett. Kinetics of Biotinyl-5'-adenylate Synthesis Catalyzed by the Escherichia coli Repressor of Biotin Biosynthesis and the Stabiliby of the Enzyme-Product Complex. Biochemistry. 1994, 33: 7354-7360
227. Yanisch-Perron C. et al. Improved MB phage cloning vectors and host strain:
nucleotide sequences of the MB mp18 and PVC19 vectors. Gene. 1985, 33:103-119
228. Yonngman, P.J. et al. Construction of a cloning site near one end of Tn917 into which foreign DNA may be inserted without affecting transposition in Bacillus subtilis or expression of the transposon-borne erm gene. Plasmid. 1984, 12:1-9
229. Yoshihito I Kariyama et al. Sensitive Bioaffinity Sensor with Metastable Molecular Complex Receptor and Enzyme Amplifier. Anal. Chem. 1985, 57:496-500
230. Yoshio Komura et al. Molecular Cloning and Characterization of Two Genes for the Biotin Carboxylase and carboxyltransferase Myxococcus Xanthus. Journal of Bacteriology. 2000, 182 (19): 5462-5469
231. You-Sheng Chang, David Shiuan. Construction and Characterization of A Biotion-Regulated Gene Expression System in Escherichia coli. Applied Biochemistry and Biotechnology. 1997, 66:147-158
232. Yu L, Bloem LJ. Use of polymerase chain reaction to screen phage libraries, in ed. White B A. prococols: A Guide to Methods and Applications in Methods in Molecular Biology. Vol 15. Totowa, NJ. Humana. 1993:211-215
233. Zhen L, Swank RT. A simple and high yield method for recovering DNA from agarose gels. BioTechniqnes, 1993, 14 (6) :894-898
234. Zintz, C. B. and Beebe, D. C. Rapid re-amplification of PCR products prified form low melting point agarose gels. Biotechniques. 1991.11: 158-162
235. Zuber, P., R. Losick. Role of AbrB in SpoOA-and SpoOB-dependent Utilization of a sporulation promoter in Bacillus subtilis. J. Bacteriol. 1987, 169:2223-2230
236．安海谦等．DNA芯片技术及其应用．生物工程进展．1998，18(2)：37
237．安利国，杨桂文．基因工程技术在免疫学中的应用．生物学通报．1999，34(7)：15-17
238．A．J．哈五德主编，DNA及RNA基本实验技术，科学出版社，2002
239．曹蕾等．肿瘤的基因治疗．科学．1998，50(1)：24
240．曹先维，张鹤龄．生物素标记核酸探针的分子杂交技术及其应用．病毒杂志．1991，6(1)：1-14
241．陈永福主编．转基因动物，科学出版社，2002，86-116
242．陈章良．生物技术前程无限，知识经济，1999，(6)：22-26
243．C．W．迪芬巴赫，G．S．德维克斯勒著．PCR技术实验指南．科学出看到社，1999
244．程度，黄翔宇，李宝健．药用真菌高质量总DNA的制备及基因组文库的构建．菌物系统．2002，21(1)：137-139
245．戴旭明，李坚，傅继梁．转基因动物的研究展望．科学时报．2002年2月13日，第4版
246．董志峰，李新萍，秦松等．基因工程与海洋药物研究．海洋科学．1998，(1)：16-20
247．段海昌．征服癌症的基因疗法．科学世界．1998．(5)：46
248．段智勇，吴跃明，刘建新．生物素对高产奶牛的作用——预防蹄病和增乳饲料研究，2003，(2)：19-21
249．鄂征主编，组织培养和分子细胞学技术，北京出版，1999
250．鄂超苏，卢运玉．一种生物素快速测定方法及其结果运算的计算机程序．微生物学报．1993，33(2)：157-160
251．方桦，张依健，李玉丰等．基因工程在家禽遗传育种中的运用．广西牧兽医．2001，17(6)：41-42
252．F．奥斯伯，R．布伦特，R．E．金斯顿等著，精编分子生物学实验指南，科学出版社，1999
253．封伟贤，王振权，峞新跃．生物素缺乏及肉鸡和种鸡日粮中添加生物素效果的研究．广西农业大学学报．1995，14(2)：157-164
254．冯建文，王凤麟．高压液相色谱法测定生物素方法的探讨．饲料工业．2002，23(7)：34-35
255．郭蔼光编著．基因工程原理与技术．西北农林科技大学．2000
256．郭葆玉主编．基因工程药学．第二军医大学出版社．2000，1-23
257．贺淹才编著．简明基因工程原理．科学出版社．1998．第一版
258．J．萨姆布鲁克等著．分子克隆实验指南(第三版)．科学出版社．2002
259．李然栋，马清霞，王昕等．新型兽用疫苗的研究现状和发展动向．中国动物检疫．2002，19(11)：38-40
260．李克明，王增力．添加生物素对产蛋鸡的效果．饲料研究．1993，(3)：2-4
261．李健，候水生，黄俊纯．肉仔鸡生物素缺乏症的观测及生物素需要量的探讨．畜牧兽医学报．1994，25(4)：295-300
262．李兰．高效液相色谱电化学检测维生素预混料中生物素含量．国外畜牧学—饲料．1998，(4)：26—27
263．李青旺，武浩编著．动物繁殖学．西安地图出版社．2000
264．李育阳主编．基因表达技术．科学出版社，2002
265．梁新梅等．d-生物素代替玉米浆发酵生产谷氨酸的研究．生物技术 1996，(2)：30-34
266．刘宝全，匡春香，范圣第等．面向21世纪的基因工程．大连民族学院学报．1999．(1)1：5-12
267．刘芝．生物技术进入后基因组时代．科技潮．2000，(8)：48-49
268．刘建军，李丕武，田延军等．基因工程技术的产生、应用及研究进展．2001，(1)：12-19
269．刘国安．基因工程与外源DNA导入技术．西北师范大学学报(自然科学版)．1999，35(4)：110-112
270．刘学剑．生物素的生理动能及其应用进展．兽药与饲料添加剂．1999，4(5)：35-36
271．刘秋云，罗樨，赫然等．一种粗糙脉孢霉菌基因组DNA的快速制备方法．生物技术．2001，11(2)：38
272．陆国权．植物基因工程技术的应用与问题．世界农业．2000，(7)：36-38
273．卢圣栋编著．现代分子生物学实验技术．高等教育出版社．1993．7
274．罗云波，黄昆仑．基因工程技术的应用现状与前景．中国科技成果，2002，(2)：14-17
275．吕健，G Rakhely,KL Kovacs等．嗜热菌Aquifex Pyrophilus中Mbh2基因簇的鉴定和部分基因的克隆及测序．微生物学报．2001，41(6)：674-679
276．马翠然，李素霞．种鸡缺生物素对孵化成绩的影响．家禽与禽病防治．1999，(8)：33
277．马大龙主编．生物技术药物．科学出版社．2001
278．彭秀玲，袁汉英，谢毅等编著．基因工程实验技术(第二版)．湖南科学技术出版社．1998
279．钱建飞，钟声．基因工程技术在畜牧兽医上的应用及展望．畜牧与兽医．1999，31(1)：41-44
280．乔建军，杜连祥．一种快速有效的枯草芽孢杆菌染色体的提取方法．生物技术．2001，11(2)：38-40
281．秦鹏春等编著．哺乳动物胚胎学．科学出版社．2001
282．瞿礼嘉，顾红雅，胡苹，陈章良编著．现代生物技术导论，高等教育出版社．1998
283．曲殿波，刘传暄，张艳红等．O_(139)霍乱弧菌质粒基因组文库的建立及O-抗原基因的筛选．微生物学报．2001，41(1)：65-69
284．沈同，王镜岩主编．生物化学(上、下册)．高等教育出版社．1991，第二版
285．盛自华．纯生物素的检测方法．发酵科技通讯．1998，72(2)：6-7，39
286．石磊，杨晓莉，王国栋等．食物和饲料中生物素的测定方法，营养学报．2002，24(2)：181—184
287．宋礼华，桂向东，徐键等．一个新的经济增长点：生物医药产业的现状和发展趋势．生物学杂志．2000，15(5)：27-30
288．孙树汉．基因工程原理与方法．人民军医出版社，2001，9-15
289．孙乃恩，孙东旭，朱德煦编著．分子遗传学．南京大学出版社．2001，470-487
290．唐冬生，夏家辉．新型基因工程药物．生命科学研究．1999，3(2)：92-95
291．唐清．大鼠AKPD基因的分子克隆研究Ⅰ．大鼠基因组文库的构建．西南民族学院学报．自然科学版．1998，24(1)：42-47
292．童克中著．基因及其表达．科学出版社，2001，274-276
293．吴瑞娟．基因工程在农业和医学上的应用．生物学通报．2000，37(4)：30-31
294．汪富泉．分子生物学与基因工程引发的思考．世界科技研究与发展．2000，22(4)：45-49
295．王保莉，巩普遍编写．生物制品概论．西北农林科技大学．2002
296．王福荣，俞津婷．生物素测定方法的研究(第Ⅰ报)．中国酿造．1992，(4)：14-18
297．王福荣，张琳，俞津婷．生物素测定方法的研究(第Ⅱ报)．中国酿造．1994，(1)：17-19
298．王福荣，俞津婷，张琳．利用异硫氰酸荧光素标记亲合素荧光法测定生物素含量．氨基酸杂志．1994，(3)：47-49
299．王和民，齐广海主编．维生素营养研究进展，中国科学技术出版社，1993
300．王军志主编．生物技术药物研究开发和质量控制．科学出版社，2002，3-74
301．王胜林．饲料添加生物素和维生素E能改善猪肉品质．兽药与饲料添加剂，2000，5(5)：28
302．王延庆，徐瑾，项坤三等．应用光敏生物素标记探针进行分子杂交的技术．中华医学遗传学杂志，1993，10(2)：104-106
303．汪永庆，王新国，徐来祥等．一种动物基因组DNA提取方法的改进．动物学杂志．2001，36(1)：27-29
304．王友明．饲料中营养物质对猪肉品质的影响．饲料研究，2000，(8)：17-18，20
305．吴乃虎编著．基因工程原理(上册)．科学出版社，2000
306．吴乃虎编著．基因工程原理(下册)．科学出版社，2001
307．伍新尧，罗超权，马涧泉主编．分子遗传学与基因工程．河南医科大学出版社．1997
308．吴冠芸，潘华珍，吴晕主编．生物化学与分子生物学实验常用数据手册．科学出版社，1999
309．吴梧桐主编．现代生化药学，中国医药科技出版社，2002
310．武英，王敬华，赵燕等．生物素对产蛋鸡生产性能的影响．中国饲料，1995，(21)：19-20
311．谢平，宋惠萍．基因工程的发展及医学意义．医学与社会，2000，(4)：3-5
312．谢庆阁．根除畜禽传染病的新对策——动物基因工程抗病育种．生物工程进展．1992，12(2)：30-33，43
313．熊辛，鄂征．生物素标记检测在基因探查中的应用．细胞生物学杂志，1990，12(4)：183-186
314．许崇任，虞建军．转基因产业的产生和发展．饲料广角．2000，(16)：10-11
315．徐幼平，陈正贤，吴建祥等．微生物发酵液中生物素含量的ELISA测定．微生物
学通报．2000，27(1)：47-50
316．徐阳．面向未来的生物技术．科学世界．1998，(3)：32
317．徐士清．基因工程与21世纪养猪业．浙江农业科学．2002，(4)：202-203
318．阎隆飞，张玉麟主编．分子生物学(第二版)．中国农业大学出版社．1997
319．严宝霞．基因与药学发展．中国医药导刊．2001，3(4)：270-273
320．严云勤，李光鹏，郑小民编著．发育生物学原理与胚胎工程．黑龙江科学技术出版社．1995
321．杨凤主编．动物营养学．中国农业出版社，1993，86
322．杨红文等，d，1-2，3，4，6-四氢-2-氧-1氢噻吩并[3，4-d]咪唑-4-戊酸的合成，化学通报，2000，(8)：34
323．杨红．用ELISA法测定基因转殖酵母菌发酵液中生物素．中国药师，2002，5(6)：351-353
324．杨吉成，缪竞诚等编著．医学基因工程．化学工业出版社，2003，16-19
325．于德强，张岚．重组药物工艺经济分析．中国生物工程杂志．2003，23(3)：85-89
326．余克伦，罗延荣．生物素标记核酸探针的应用概况，中国兽医科技．1990，(2)：17-18
327．俞键．基因工程进展与二十一世纪人类生活．天津科技．2002，29(3)：48-50
328．张惠展著．基因工程概论．华东理工大学出版社，2000
329．张明峰．动植物转基因技术育种的成就．世界农业．2000，(4)：42-43
330．张树庸．我国基因工程研究概况．实验动物科学与管理．2001，18(4)：30-33
331．张伟，周桂莲．母猪的维生素营养．养猪．2001，(1)：5-8
332．张学敏，王宜强主编．靶向新基因的分子克隆策略——理论与方法．军事医学科学出版社．1999
333．周林．生物素和维生素E对肉鸡屠宰性能和肉品质的影响．饲料博览．2000，(8)：6-7
334．周桂莲．生物素在畜禽生产中的作用．中国饲料．2000，(6)：14-15
335．祖荫光，周利．谷氨酸发酵中生物素含量的测定．发酵科技通讯．2003，32(2)：18-19
2. Allan Campbell et al. Biotin Regulator (bir) Mutations of Escherichia coli. Journal of Bacteriology. 1980,142 (3): 1025-1028.
3. Andrea Pimenta et al. To be free or not: the fate of pimelate in Bacillus sphaericus and in Escherichia coli. Molecular Microbiology. 1995, 19:639-647
4. Andree Marquet et al. Biosynthesis of Biotin and Lipoic Acid. Vitamins and Hormones.2001, 61:51-101
5. Annick Mejean et al. Highly Purified Biotin Synthase Can Transform Dethiobiotin into Biotin in the Absence of Any Other Protein, in the Presence of Photoreduced Deazaflavin. Biochemical and Biophysical Research Communications. 1995, 217 (3) :1231-1237
6. Anthony J et al. The Escherichia coli Biotin Biosynthetic Enzyme Sequence Predicted from the Nucleotide Sequence of the bio operon. The Journal of Biological Chemistry.1988,263(36):19577-19585
7. Anthony Otsuka, John Abelson et al. The regulator region of the biotin operon in Escherichia coli. Nature. 1978.276:689-694
8. Ayumi Fujisawa et al. Biotin Production by bioB Transformants of a Bacillus sphaericus Mutant Resistant to 1-(2'-Thenoyl)-3, 3, 3-trifluoroacetone, an Electron Transport Inhibitor. Biosci. Biotech. Biochem. 1994.58(6): 1018-1022
9. Azevedo, V. et al. The transcriptional organization of the Bacillus subtilis 168 Mol.Microbiol. 1993, 10:397-405
10. Barbara Hartl et al. Development of a New Integration Site within the Bacillus subtilis Chromosome and Construction of Compatible Expression Cassettes. Journal of Bacteriology. 2001, 183 (8):2696-2699
11. Barnes WM. PCR amplification of up to 35 kb with high fidelity and high yield form λ bacteriophage templates. Proc Natl Acad Sci USA, 1994, 91:2216-2220
12. Bartra Sk. et al. A simple, effective method for the construction of subtracted cDNA libraries. Gene Anul Technol. 1991, 8:129-133
13. Batzer MA. et al. Enhanced evolutionary PCR using oligonucleotides with inosine at the 3'-terminus. Nucleic Acids Res, 1991, 91:5081
14. Bell DA, Demarini D. Excessive cycling converts PCR products to random-length higher molecular weight fragments. Nucleic Acids Res, 1991, 91:5079
15. Bhat GJ et al. A simple method for cloning blunt ended DNA fragments. Nucleic Acids Res, 1991, 19:398
16. Birch, O. M. et al. Biotin synthase from Escherichia coli, an investigation of the low molecular weight and protein components required for activity in vitro. J. Biol. Chem. 1995, 270:19158-19165
17. Blumberg DD. Creating a ribonuclease free environment, Methods Enzvmol, 1987, 152: 20-24
18. Bokhee Kim et al. Adapting homogeneous enzyme-linked competitive binding assays to microtiter plates. Analytical Biochemistry. 1994, 218:14-19
19. Bower, S. et al. Biotin biosynthesis in Bacillus subtilis. European patent application 1994, 94108998.9
20. Brown, T. A., ed. Molecular Biology Labfax. BIOS Scientific Publishers. Oxford, 1991
21. Burke, D. T. et al. Cloning of large segments of exogenous DNA into yeast by means of artificial chromosome vectors. Science, 1987.236:806-812
22. Calvin, N. M. and Hanawalt P. C. High efficiency transformation of bacterial cells by electroporation. J. Bacteriol. 1988.170:2796-2801
23. Cha J. et al. New vectors for direct cloning of PCR products, of 1993, 136:369-370
24. Cheng S, Chang SY, Gravitt P, Respess R. Long PCR. Nature, 1994, 369:684-685
25. Cheng S, Fockler C, Barnes WM et al. Effective amplification of long targets from cloned inserts and human genomic DNA. Proc Natl Acad Sci USA, 1994, 91:5695-5699
26. Cheng S, Higuchi R, Stoneking M. Complete mitochondrial genome amplification.Nature Genet, 1994, 7:350-351
27. Cheng S. et al. Template integrity is essential for PCR amplification of 20-to 30-kb sequences from genomic DNA. PCR Meth Appl, 1995, 4:294-298
28. Cheng S. Longer PCR amplifications in eds. Innis MA, Gelf and DH, Sninsky JJ. PCR Strategies, San Diego, CA: Academic, 1995:313-324
29. Chou Q. et al. Prevention of pre-PCR mis-priming and primer dimerization improves low copy number amplifications. Nucleic Acids Res, 1992, 20:1717-1723
30. Church DM. et al. Isolation of genes from complex sources of mammalian genomic DNA using exon amplification. Nature Genet. 1994, 6: 98-105
31. Chwen-Huey Wu et al. Isolation and characterization of the Erwinia herbicola bio operon and the sequences of the bioA and bioB genes. Gene. 1996, 174:251-258
32. Chwen-Huey Wu et al. Molecular Cloning and Nucleotide Sequencing of BioF (7-Keto-8-Amino Pelargonic Acid Synthetase), BioC and BioD (Dethiobiotin Synthetase) Genes of Erwinia Herbicola. Biochemistry and Molecular Biology International. 1997, 41 (2):311-315
33. Clark JM. Novel non-template nucleotide addition reactions catalysed by procaryotic and eucaryotic and eucaryotic DNA polymerase. Nucleic Acids Res. 1988, 20:9677-9686
34. Costa GL, Weiner Mp. Protocols for cloning and analysis of blunt-ended PCR-generated DNA fragments. PCR Meth Appl, 1994, 3: S95-S106
35. D, Souza CR et al. A simplifed procedure for cDNA and genomic library construction using nonpalindromic oligonucleotide adaptors. Biochem cell Biol. 1989.67:205-209
36. D. Speck et al. Isolation of Bacillus sphaericus biotih synthesis control mutants: evidence for transcriptional regulation of bio genes. Gene. 1991, 108: 39-45
37. D' Aquila RT et al. Maximizing sensitivity and specificity of PCR by preamplification heating. Nucleic Acids Res. 1991.19:37-49
38. David A. Patton et al. An Embryo-Defective Mutant of Arabidopsis Disrupted in the Final Step of Biotin synthesis. Plant Physiol. 1998, 116:935-946
39. David A. Patton et al. Complementation of an Arabidopsis thaliana biotin auxotroph with an Escherichia coli biotin biosynthetic gene. Mol Gen Genet. 1996, 251: 261-266
40. David F. Barker et al. Sequence and properties of operator mutations in the bio operon of Escherichia coli. Gene. 1981, 13:89-102
41. David F. Barker et al. Use of bio-lac Fusion Strains to Study Regulation of Biotin Biosynthesis in Escherichia coli. Journal of Bacteriology. 1980, 143(2): 789-800
42. David Shiuan et al. Transptional analysis of the Escherichia coli bio operon. Gene.1994, 145: 1-7
43. David Shiuan, Allan Campbell. Transcriptional regulation and gene arrangement of Escherichia coli, citrobacter freundii and Salmonella typhimurium biotin operons.Gene. 1988, (67) :203-211
44. Davis LG. et al.Basic Methods in Molecular Biology. New York: Elsevier, 1986
45. De Leenheer AP et al. Modern chromatographics analysis of the vitamins, New York: Marcol Dekoker, 1985:447
46. Delidow BC. Molecular Cloning of polymerase chain reaction fragments with cohesive ends, in ed. White BA. PCR Protocols: Current Methods and Applications. Totowa, NJ. Humana, 1993:217-228
47. Denman, J., M. Hayes and C. O. Day, et al. 1991. Transgenic expression of a variant of
human tissue-type plasminogen activator in goat milk: purification and characterization of the recombinant enzyme. Biotechnology,9:839～843
48. Dmitry A. Rodionov et al. Conservation of the biotin Regulation and the BirA Regulatory signal in Eubacteria and Archaea. Genome Research. 2002, 12:1507-1516
49. Dominique Florentin et al. On the mechanism of biotin synthase of Bacillus sphaericus. C. R. Acad. Sci Paris, Science de la vie/life sciences. 1994, 317:485-488
50. Don RH. et al. 'Touchdown' PCR to circument spurious priming during gene amplification. Nucleic Acids Res, 1991, 19:4008
51. Donald M. Mock et al. A Fluorometric Assay for the biotin-Avidin Interaction Based on Displacement of the Fluorescent Probe 2-Anilinonaphthalene-6-sulfonic Acid. Analytical Biochemistry. 1985.151: 178-181
52. Dorothy Beckett. [21] Energetic Methods to study Bifuctional Biotin Operon Repressor.Methods in Enzymology. 1998, 295:424-451
53. Dower, W. J. et al. High efficiency transformation of E. coli by high voltage electroporation. Nucl. Acids. Res. 1988.16:6127-6145
54. Dycaico M et al. Reduce PCR false positives using the Stratalinker UV crosslinker. Stratagene Strategies, 1991, 4(3): 39-40
55. E. Joan William and Anthony K. Campbell. A Homogeneous Assay for bioth Based on chemiluminescence Energy Transfer. Analytical Biochemistry. 1986. 155:249-255
56. Ebert, K. M., M. J. Low and E. W. Overstrom et al. 1988. A moloney MLV-rat somatotropin fusion gene produces biologically active domatotropin in a transgenic pig. Mol. Endocrin, 2:277～283
57. Edward A. Bayer et al. A Sensitive Enzyme Assay for Biotin, Avidin, and Streptavidin.Analytical Biochemistry. 1986. 154:367-370
58. Edward Demol and William Shive. Assay for Biotin in the presence of Dethiobiotin with Lactocacillus Plantarum. Analytical Biochemistry. 1986. 158:55-58
59. Edward Eisenstein et al. Dimerization of the Escherichia coli biotin repressor:corepressor function in protein assembly. Biochemistry, 1999, 38:13777-13804
60. Eisenbery, M. A. Biosynthesis of biotin and lipoic acid, P.554-560.In F. C. Neidhardt. J. L. Ingraham, B. et al. Escherichia coli and Salmonella typhimurium: cellual and molecular biology. American Society for Microbiology, Washington, D. C.
61. Elizabeth H. et al. A physical map of the Escherichia coli bio operon. Gene. 1982.19:93-103
62. Emily D. Streaker, Dorothy Beckett. Coupling of Site-Specific DNA Binding to Protein Dimerization in Assembly of the Biotin Repressor-Biotin Operator Complex.
Biochemistry. 1998, 37, 3210-3219
63. Erlich HA et al. Recent advances in the ploymerase chain reaction, Science. 1991, 252:1643-1651
64. Errington, J. Efficient Bacillus subtilis cloning system using bacteriophage vector φ 10591. Journal of General Microbiology, 1984, 130:2615-2628
65. Evangelia Livaniou et al. Analytical techniques for determining biotin. Journal of Chromatography A. 2000, 881:331-343
66. F. kunst et al. The complete genome sequence of the Gram-positive bacterium Bacillus subtilis. Nature. 1997. 390:249-256
67. Florentin, D. et al. On the mechanism of biotin synthetase of Bacillus Spaericus. C. R. Acad. Sci. Ser. III 317:485-488
68. Forrester HB. et al. Amplification of Low copy number, large DNA sequences in human genomic DNA using Tub DNA polymerase. Biotechniques, 1994, 17:20-22
69. Friedmann KD. et al. Enzymatic amplification of specific cDNA inserts from λ gt11 libraries.Nucleic Acids Res. 1988.16: 8718
70. FrischaufAM. Construction and characterization ofa genomic library in λ. Methods Enzyzmol,1987, 152:190-199
71. Gary Ketner, Allan Campbell et al. Operator and Promoter Mutations Affecting Divergent Transcription in the bio Gene Cluster of Escherichia coli. J. Mol. Biol. 1975,96:13-27
72. Gibson. K. J. et al. Dethiobiotin Synthetase: the carbonylation of 7, 8-diaminononanoic acid proceeds regiospecifically via the N7-carbamate. Biochemistry. 1995, 34: 10976-10984
73. Gossler, A.and R. Ralling. 1992. The molecular and genetic analysis of mouse development. Eur. J. Biochem., 204:5～11 Grosveld, E. and G. Kollias. 1992. Transgenic animals. Academic Press
74. Grazyna Konopa et al. A physical map of the bioAB region in the λ bio transducing phage. Gene. 1982. 19:104-108
75. Gunter Schneider, Ylva Lindqvist. Structural enzymology of biotin biosynthesis. FEBS Letters. 2001, 495:7-11
76. Gussow D, Clackson T. Direct clone characterization from plaques and colonies by the polymerase chain reaction. Nucleic Acids Res, 1989, 17:4000
77. Hammer, R.E., V. G. Pursel and C. E. Rexroad et al. 1985. Production of transgenic rabbits, sheep and pigs by microinjection. Nature, 315:680～683
78. Hanahan D. Studies on transformation of E. coli with plasmids. J Mol Biol. 1983. 166:
557-580
79. Harrison J et al. Direct cloning of polymerase chain reaction products in an XcmI T-vecter. Anal Biochem, 1994, 216:235-236
80. Hartmut R. Schroeder et al. Competitive protein binding assay for biotin monitored by chemiluminescence. Analytical Chemistry. 1976, 48 (13): 1933-1937
81. Harwood, C. R. et al. Growth, maintenance and general techniques, P. 7. In C. R. Harwood and S. M. Cutting (ed.), Molecular biological methods for Bacillus. John Wiley & Sons, Chichester, England 1990.
82. Haymerle H et al. Efficient construction of cDNA libraries in plasmid expression vectors using an adapter strategy. Nucleic Acids Res. 1986, 14:8615-8624
83. Hecker KH, Roux KH. High and low annealing temperatures increase both specificity and yield in TD and SD PCR. Biotechniques, 1996, 20:478-485
84. Heery DM et al. A simple method for subcloning DNA fragments from gel slices. Trends Genet. 1990, 6:173
85. Hideaki Yamada et al. Biotin Overproduction by Bioth Analog-resistant Mutants of Bacillus sphaericus. Agric. Biol. Chem. 1983, 47(5): 1011-1016
86. Holland PM et al. Detection of specific polymerase chain reaction product by utilizing the 5'-3' exonuclease activity of Thermus aquaticus DNA polymerase. Proc Natl Acad Sci USA, 1991, 88:7276-7280
87. Holton TA, Graham MW.A simple and efficient method for direct cloning of PCR products using ddT-tailed vectors. Nucleic Acids Res, 1991, 19:1156
88. Horton RM, Hoppe BL, Conti-Tronconi BM. AmpliGrease, "Hot Start" PCR using petroleum jelly. Biotechniques, 1994, 16:42-43
89. Hu G. DNA polymerase-catalyzed addition of nontemplated extra nucleotides to the 3' end of a DNA Fragmet. DNA cell Biol, 1993, 12:763-770
90. Huang SH, et al. Amplification of gene ends from gene libraries by PCR with single-sided specificity. Methods Mol Biol. 1993, 15:357-363
91. Huang W. et al. Mechanism of an ATP-dependent carboxylase, dethiobiotin synthetase, based on crystallographic studies of complexes with substrates and a reaction intermediate. Biochemistry. 1995, 34:10985-10995
92. Hueck, C. J., W. Hillen. Catabolite repression in Bacillus subtilis: a global regulatory mechanism for the gram-positive bateria? Mol. Microbiol. 1995, 15:395-401
93. I chihara Y, kurosawa Y. Construction of new T vectors for direst cloning of PCR products. Gene, 1993, 130:153-154
94. I ohsawa et al. Cloning of the biotin synthetase gene from Bacillus sphaericus and
expression in Escherichia coli and Bacilli. Gene, 1989, (80): 39-48
95. Ifuku O. et al. Flavodovin is required for conversion of dethiobiotin to biotin in Escherichia coli. Eur. J. Biochem. 1994, 224:173-178
96. Ifuku, O. et al. Conversion of dethiobiotin to biotin in cell-free extracts of Escherichia coli. Bioci. Biotechnol. Biochem. 1992, 56:1780-1785
97. Ilya G. Serebriiskii et al. Two new members of the BioB superfamily: cloning, Sequencing and expression of bioB genes of Methylobacillus fiagellatum and Corynebacterium glutamicum. Gene. 1996, 175: 15-22
98. Indrajit Sanyal et al. Escherichia coli Biotin Synthase: An Investigation into the Factors Required for Its Activity and Its Sulful Donor. Archives of Biochemistry and Biophysics. 1996. 326(1): 48-56
99. Inoue, H. et al. High efficiency transformation of Echerichia coli with plasmids. Gene.1990, 96:23-28
100. Isola NR. et al. Screening recombinant DNA libraries: a rapid and efficient method for isolating cDNA clones utilizing the PCR. BioTechniques. 1991.11:580-582
101. Iwahana H et al. T-cassette ligation: a method for direct sequencing and cloning of PCR-amplified DNA fragments. PCR Methods Applic. 1994, 3:219-224
102. Jeanette E Stok, James J. De Voss. Expression, Purification, characterization of BioI: A Carbon-Carbon Bond Cleaving Cytochrome P450 involved in Biotin Biosynthesis in Bacillus subtilis. Archives of Biochemistry and Biophysics. 2000, 384(2): 351-360
103. Jennifer Abbott, Dorothy Beckett. Cooperative Binding of the Escherichia coli Repressor of Biotin Biosynthesis to the Biotin Operon Sequence. Biochemistry. 1993, 32, 9649-9656
104. Jepson I et al. A rapid procedure for the construction of PCR cDNA libraries from small amounts of plant tissue. Plant Mol Biol Reporter. 1991, 9:131-138
105. Jeroo Kotval et al. Leftward transcription in the Escherichia coli bio operon does not require products of the right word transcript. Gene. 1982, 17:219-222
106. John B. Perkins et al. Indentification and characterization of transcriptions from the biotin biosynthetic operon of Bacillus subtilis.Journal of Bacteriology. 1996.178(21);6361-6365
107. John E. cronan, Jr. Expression of the biotin Biosynthetic Operon of Escherichia coli Is Regulated by the Rate of Protein Biotination. The Journal of Biological Chemistry.1988, 263(21):10332-10336
108. John E. Cronan, Jr., The E. coli bio operon: Transptional Repression by an Essential Protein Modification Enzyme. Cell 1989, 58:427-429
109. John T. Sullival et al. The bio operon on the acquired symbiosis island of Mesorhizobium sp. Strain R7A includes a novel gene involved in pimeloyl-coA synthesis. Microbiology, 2001, 147:1315-1322
110. John T. Sullivan et al. The bio operon on the acquired symbiosis island of Mesorhizobium Sp. Strain RTA includes a novel gene involved in pimeloyl-CoA synthesis. Microbiology. 2001, 147:1315-1322
111. Kaiser, K. and Murray, N. E. The use of phage lambda replacement vectors in the construction of representative genomic DNA libraries. In DNA cloning: A practical Approach, vol. 1 (D.M. Glover, ed. )PP. 1-47. IRL Press, Oxford. 1984
112. Kaith J. Schray and Pamela G. Artz. Determination of Avidin and Biotin by Fluorescence Polarization. Anal. Chem. 1988, 60:853-855
113. Kaufman DL, Evans GA. Restriction endonuclease cleavage at the termini of PCR products. Biotechniques, 1990, 9:305-306
114. Keehwan Kwon et al. Multiple disordered loops function in corepressor-induced dimerization of the biotin repressor. J. Mol. Biol. 2000, 304:821-833
115. Keith P. Wilson et al. Escherichia coli biotin holoenzyme synthetase/bio repressor crystal structure delineates the biotin- and DNA-binding domains. Proc. Natl. Acad. Sci. USA. 1992, 89:9257-9261
116. Kevin M. Vchida, Anthony J. Otsuka. Isolation and characterization of Escherichia coli birA intragenic suppressors. Mol Gen Genet 1987, 210:234-240
117. Kinttel T, Picard D. PCR with degenerate primers containing deoxyinosine fails with pfu DNA polymerase. PCR Meth Applic, 1993, 2:346-347
118. Kogl F. Uber Wuchsstoffe der Auxin-under Biosgurppe. Ber, 1935, 68A: 16(CA,1935, 29: 2563)
119. Kolmodin L et al. GeneAmp XL PCR kit. Amplification: A Forum for PCR users (The Perkin-Elmer coporation), 1995, 13:1-5
120. Kovalic D et al. General method for direct cloning of DNA fragments generated by the polymerase chain reaction. Nucleic Acids Res, 1991, 19:4560
121. Kripamoy A et al. An improved method for the construction of high efficiency cDNA library in plasmid or lambda vector Nucleic Acids Res. 1990, 18:1071
122. Kuo-Chih Lin et al. Binding characteristics of Escherichia coli biotin repressor-operator complex. Biochimica et Biophysica Acta. 1991, 1090:317-325
123. Kwok S, Higuchi R. Avoiding false positives with PCR. Nature. 1989. 339:237-238
124. Lardelli M, lendahl U. Generating bacteriophge λ sublibraries enriched for rare clones. BioTechniques. 1994, 16:420-422
125. Larry H. Weaver et al. Corepressor-induced organization and assembly of the biotin repressor: A model for allosteric activation of a transcriptional regulator. Proc. Natl. Acad. Sci. USA, 2001, 98(11): 6045-6050
126. Lau EC et al. Preparation of denatured plasmid templates for PCR amplification.Biotechniques. 1993, 14:378
127. Lauer, G. et al. Cloning, nucleotide sequence, and engineered expression of Thermus thermophilus DNA ligase, a homolog of Ecsherichia coli DNA ligase. J. Bacteriol. 1991, 173:5047-5053
128. Lemoine, Y. et al. To be free or not: the fate of pimelate in Bacillus sphaericus and in Escherichai coli. Mol. Microbiol. 1996. 19:645-647
129. Lerner, C. G., M. Inonye. Low copy number plasmids for regulated Low-lever expression of cloned genes in Escherichia coli with blue/white insert screening capability. Nucleic Acids Res. 1990. 18:4631
130. Lisa M. Weaver et al. Characterization of the cDNA and Gene Coding for the Biotin Synthase of Arabidopsis thaliana. Plant Physiol. 1996, 110:1021-1028
131. Lisa McIver et al. Indentification of the [Fe-s] cluster-binding residues of Escherichia coli biotin synthase.The Journal of Biological Chemistry, 2000, 275(18): 13888-13894
132. Luo MZ, Cella R. A reliable amplification technique with single-sided specificity for the isolation of 5'gene regulating region. Gene. 1994, 140:59-62
133. Lynn Farh et al. Structure-Fuction Studies of Escherichia coli Biotin Approach. J. Biochem. 2001, 130:627-635
134. M. Friggs et al. Biotin inclusion helps optimize animal performance. Feedstuffs. 1994, (1): 12-13
135. Maloy, S. R. Experimental techniques in bacterial genetics, P.48. Jones and Bartlett Publishers, Boston. 1990.
136. Marchuk D. et al. Construction of T-vectors, a rapid and general system for direct cloning of unmodified PCR products. Nucleic Acids Res, 1991, 19:1154
137. Martin R. Buoncristaini, Anthony J. Otsuka. Overproduction and Rapid purification of the Biotin Operon Repressor from Escherichia coli. The Journal of Biologcal Chemistry. 1988, 263(2): 1013-1016
138. Martin R. Buoncristiani et al. DNA-binding and enzymatic domains of the bifunctional biotin operon repressor (BirA) of Escherichia coli. Gene. 1986, 44:255-261
139. Max A. Eisenbery et al. Mode of Action of the Biotin Antimetabolites Actithiazic
Acid and α-Methyldethiobiotin. Antimicrobial Agents and chemotheraphy. 1982,21(1):5-10
140. Mead DA et al. A universal method for the direct cloning of PCR amplified nucleic acid. Bio/Technology, 1991, 9:657
141. Meissner PS et al. Bacteriophage lambda cloning system for the construction of directional cDNA libraries. Proc Natl Acad Sci USA, 1987, 84:4171-4175
142. Messing J. New M13 vectors for cloning. Methods Enzymol. 1983, 101:20-78
143. Michael Young et al. Gene Amplification in Bacillus subtilis. Journal of General Microbiology. 1984, 130:1613-1621
144. Monforte JA et al. Megabase genomic DNA isolation procedure for use in transgenic mutagenesis assays. Environ Mol Mutagenesis 1994, 23:46
145. Mullis KB et al. eds. The polymerase Chain Reaction. Boston, MA: Birkhauser, 1994
146. Mullis KB, Erlich HA. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988, 239:487-491
147. Munroe DJ et al. Systematic screening of an arrayed cDNA library by PCR. Proc Natl Acad Sci USA. 1995.92:2209-2213
148. N M Shaw et al. Biotin production under limiting growth conditions by Agrobacterium/Rhizobium HK4 transformed with a modified Escherichia coli bio operon. Journal of Industrial Microbiology & Biotechnology. 1999, 22:590-599
149. Naoki Sakurai et al. Complete Sequence and organization of the serratia marcescens biotin operon. Microbiology, 1996, 142: 3295-3303
150. Naoki Sakurai et al. Construction of a Biotin-Overproducing Strain of Serratia marcescens. Applied and Environmental Microbiology. 1993, 59 (9) :2857-2863
151. Naoki Sakurai et al. Instability of the mutated biotin operon plasmid in a biotin-producing mutant of Serratia marcescens, Journal of Biotechnology. 1995 (43) :11-19
152. Naoki Sakurai et al. Molecular Breeding of a Biotin-Hyper producing Serratia marcescens Strain.Applied and Environmental Microbiology. 1993, 59 (10):3225-32312
153. Naotake Ogasawara. Systematic function analysis of Bacillus subtilis genes. Res. Microbiol. 2000, 151: 129-134
154. Natalia B. et al. Biotin Synthase Contains Two Distinct Iron-Sulfur Cluster Binding Sites: Chemical and Spectroelectrochemical Analysis of Iron-Sulfur Cluster Interconversions. Biochemistry. 2001, 40:8343-8351
155. Nicholas H. Tomczyk et al. Purification and characterization of the BIOH proteim
from the biotin biosynthetic pathway. FEBS letters. 2002, 513:299-304
156. Nicholas M. Shaw et al. Biotin synthase from Escherichia coli: isolation of an enzyme-generated intermediate and stoichiometry of s-adenosylmethionine use. Biochem J. 1998.330:1079-1085
157. Nickloff, J. A. and Reynolds, R. J. Subcloning with new ampicillin and kanamycin resistant analogs of pUC19. Biotechniques. 1991.10:469-472
158. Nyles W. Charon et al. Isolation of Lambda Transducing Phage with the bio Genes Inserted Between Lambda Genes P and Q. Genetics. 1980, 95: 1-13
159. Ohji Ifuku et al. Molecular Analysis of Growth Inhibition Caused by Overexpression of the Biotin Operon in Escherichia coli. Bioci. Biotech. Biochem. 1995, 59(2):184-189
160. Ohji Ifuku et al. Origin of carbon atoms of biotin ~(13)C-NMR studies on biotin biosynthesis in Escherichia coli. Eur. J. Biochem. 1994, 220:585-591
161. Ohji Ifuku et al. Sequencing Analysis of Mutation Points in the Biotin Operon of Biotin-overproducing Escherichia coli Mutants. Biosci. Biotech. Biochem. 1993, 57 (5) :760-765
162. Olivier ploux et al. Mechanistic studies on the 8-amino-7-oxopelargonate synthase, a pyridoxal-5'-phosphate-dependent enzyme involved in biotin biosynthesis. Eur. J. Biochem. 1996. 236:301-308
163. OM Prakash, Max A. Eisenberg. In vitro synthesis and Regulation of the Biotin Enzymes of Escherichia coli K- 12. Journal of Bacteriology. 1978, 134 (3): 1002-1012
164. Palmer, M.S., A. H. Sinclair and P. Berta et al. 1989. Genetic evidence that ZFY is not the testis determing factor. Nature, 342:937～939
165. Palva, I. Molecular cloning of α-amylase gene form Bacillus amyloliquefaciens and its expression in B. subtilis. Gene, 1982, 19:81-87
166. Parimoo S et al. cDNA selection: efficient PCR approach for the selection of cDNAs encoded in large chromosomal DNA fragments. Proc Natl Acad Sci USA. 1991.88: 9623-9627
167. Patanjali SR et al. Construction of a uniform-abundance (normalised) cDNA library. Proc Natl Acad Sci USA. 1991. 88:1943-1947
168. Patil RV, Dekker EE. PCR amplification of an Escherichia coli positions in degenerate amino acid codons. Nucleic Acids Res, 1990, 18:3080
169. Paul A. Smith et al. A plasmid expression system for quantitative in vivo biotinylation of thioredoxin fusion protein in Escherichia coli. Nucl. Acids. Res. 1998, 26(6):1414-1420
170. Perkins, J. B. and J. G. Pero. Biosynthesis of riboflavin, biotin, folic acid, and Cobalamin, P. 319-334. In A. L. Sonenshein, J. A. Hoch, and R. losick (ed.). Bacillus subtilis and other gram-positive bacteria: biochemistry, physiology, and molecular genetics. American Society for Microbiology, Washington, D. C.
171. Peter K. Howard et al. Nucleotide sequence of the birA gene synthetase functions of Escherichia coli. Gene. 1985, 35:321-331
172. Pierce JC et al. A positive selection vector for cloning high molecular weight DNA by the bacteriophage P1 system: improved cloning efficacy. Proc Natl Acad Sci USA. 1992.89-2056-2060
173. Pierre Baldet et al. Biotin synthesis in higher plant: Purification and charaterization of bioB gene product equivalent from Arabidopsis thaliana overexpressed in Escherichia coli and its subcellular localization in Pea leaf cells. FEB S letter. 1997.419:206-210
174. Plamena Entcheva et al. Fuctional Analysis of Sinorhizobium Meliloti Genes Involved in Biotin Synthesis and Transport. Applied and Environmental Microbiology.2002, 68(6): 2843-2848
175. Ploux, O. et al. Investigations of the first step of biotin biosynthesis in Bacillus sphaericus. Purfication and characterization of the pimeloyl-CoA Synthetase and uptake of pimelate. Biochem. J. 1992.287:685-690
176. Ploux, O. et al. The 8-amino-7-oxoate pelargon synthase from Bacillus sphaericus. Pruification and preliminary characterization of the cloned enzyme overproduced in Escherichia coli. Biochem J. 1992, 283: 321-327
177. Pouwels, P. H. et al. Cloning Vectors: A Laboratory manual. Elsevier Science Publishing, Amsterdam, 1985
178. R. Alonso et al. Rapid extraction of high purity chromosomal DNA form serratia marcescens. Letters in Applied Microbiology. 1993.16:77-79
179. R. Gleockler et al. Cloning and characterization of the Bacillus spaericus genes controlling the bioconversion of pimelate into dethiobiotin. Gene. 1990, 87:63-70
180. Ralph W. et al, Bacteriocins of Gram-Positive Bacteria Microbiological Reviews. 1995, 59(2): 171-200
181. Richard G. Brennan et al. Crystallization of the Bifunctional Biotion operon Repressor. The Journal of Biological Chemistry. 1989, 264 (1) :5
182. Roux KH. Optimization and troubleshooting in PCR. PCR Meth Applic, 1995, 4:S185-S194
183. Rychlik W. New algorithm for determining primer efficiency in PCR and sequencing. J NIH Res, 1994, 6:78
184. Rychlik W. Selection of primers for polymerase chain reaction. In ed. White BA, PCR Protocols: A Guide to Methods and Applications. in methods in Molecular Biology.Vol. 15, NJ:Humana, Totowa, 1993:31-40
185. S. A. Halvatzis and Timotheou-potamia. Kinetic-potentiometric determination of ascorbic acid, biotin, pyridoxine hydrochloride and thiamine hydrochloride with N-bromosuccinimide. Analytical Chimica Acta. 1989, 227:405-499
186. S. A. Yankofsky et al. Solid-Phase Assay for d-Biotin on Avidin-cellulose Disks. Analytical Biochemistry. 1981, 118:307-314
187. S. W. Brown et al. The production of Biotin by Recombinant strains of Escherichia coli. J. Chem. Tech. Biotechnol. 1991, 50:115-121
188. Sambrook J. et al. Molecular cloning: A Laboratory Manual, 2nd eds. Cold Spring Harbour, NY: Cold Spring Harbor Laboratory, 1989
189. Sandhu GS et al. Rapid one-step characterization of recombinant vectors by direct analysis of transformed Escherichia coli colonies. BioTechniques. 1989.7:689-690
190. Sanyal I. et al. Biosynthesis of pimeloyl-CoA, a biotin precursor in Escherichia coli, follows a modified fatty acid synthesis pathway: ~(13)C-labeling studies. J. Am. Chem.Soc. 1994, 116:2637-2638
191. Sanyal I. et al. Biotin synthase: purification, characterization as a [2Fe-2S] cluster protein, and in vitro activity of the Escherichia coli bioB gene product. Biochemistry. 1995, 33:3625-3631
192. Sanyal I. et al. Escherichia coli biotin synthase: an investigation into the factors required for its activity and its sulfur donor. Arch. Biochem. Biophys. 1996, 326: 48-56
193. Scharf SJ. et al. Direct cloning and sequence analyses of enzymatically amplified genomic sequences. Science, 1986, 233:1076-1078
194. Shuguang Zhang et al. The Gene for Biotin Synthase from Saccharomyces cerevisiae: Cloning, Sequencing, and Complementation of Escherichia coli Strains Lacking Biotin Synthase. Archives of Biochemistry and Biophysics. 1994. 309 (1) :29-35
195. Shyamala U, Ames GFL. Genome walking by single-specific primer polymerase chain reaction: ssp-PCR. Gene. 1989, 84:1-8
196. Stanley Bower et al. Cloning and Characterization of Bacillus subtilis birA gene Encoding a Repressor of the Biotin operon. Journal of Bacteriology. 1995, 177 (19) :2572-2575
197. Stanley Bower et al. Cloning, Sequencing and Characterization of the Bacillus subtilis Biotin Biosynthetic Operon. Journal of Bacteriology, 1996, 178 (14): 4122-4130
198. Stephen W. Brown, K. Kamogawa. The Production of Biotin by Genetically Modified Micro-organisms. Biotechnology and Genetic Engineering Reviews. 1991, 9:295-326
199. Steven W. Polyak et al. Biotin Protein Ligase from Saccharomyces Cerevisiae The N-Terminal Domain is Required for Complete Activity. J Biol Chem. 1999, 274: 32847-32854
200. Stewart ACM et al. Generation of entire human papilloma virus genomes by long PCR: frequency of errors produced during amplification. Genome Res, 1995, 5:79-88
201. Stoker AW. Cloning of PCR products after defined cohesive termini are created with T_4 DNA polymerase. Nucleic Acids Res. 1990. 18:4290
202. Struhl K. Arapid method for creating recombinant DNA molecules. BioTechniques.1985.3:452-453
203. Suggs SV et al. Use of synthetic oligodeoxyribonucleotides for the isolation of specific cloned DNA sequences. In eds. Brown DD. Fox GF, Developmental Biology Using Purified Genes. New York: Academic. 1983:683-693
204. Swanson, M.E., M. J. Martin and J.K. O'Donnell et al. 1992. Production of functional human hemoglobin in transgenic swine. Biotechnology, 10:557-559
205. Swapan K. Nath, Arabinda Guha. Abortive termination of bioBFCD RNA synthesized in vitro from the bioABFCD operon of Escherichia coli K-12. Proc. Natl. Acad. Sci. USA. 1982, 79:1786-1790
206. Swapan K. Nath. Attenuation of transption of biotin genes in Escherichia coli. Can. J. Microbiol. 1988, 34:1288-1296
207. Sylvia Daunert et al. Pyruvate carboxylase as a Model for oligosubstituted emzyme-ligand conjugate in homogeneous emzyme immunoassays. Anal. Chem.1989, 61:2160-2164
208. Takashi Ohshiro et al. Enzymatic Conversion of Dethiobiotin to Biotin in cell-free Extracts of a Bacillus sphaericus bioB Transformant. Biosci. Biotech. Biocheml. 1994, 58(9): 1738-1741
209. Takumi T, Lodish HF. Rapid cDNA cloning by PCR screening. BioTechniques. 1994.17:443-444
210. Tatsuya Kiyasu et al. Cloning and characterization biotin biosynthetic genes of kurthia sp. Gene. 2001, (265): 103-113
211. Tatsuya kiyasu et al. Contribution of Cysteine Desulfurase (Nifs Protein) to the Biotin Synthase Reaction of Escherichia coli. Journal of Bacteriology, 2000, 182 (10):2879-2885
212. Testori A et al. Driect cloning of unmodified PCR products by exploiting an
engineered restriction site. Gene, 1994, 143: 151-152
213. Triglia T et al. A procedure for in vitro amplification of DNA segments that lie outside the boundaries of known sequences. Nucleic Acids Res. 1988.16:8186
214. Troutt AB et al. Ligation-anchored PCR: a simple amplification technique with single-sided specificity. Proc Natl Acad Sci USA. 1992.89:9823-9825
215. Tsuguchika Yoshida et al. Liquid chromatographic determination of biotin by using 1-phrenyldlazomethane as a pre-column fluorescent labeling reagent. Journal of chromatography. 1988.456:421-426
216. Unrau P, Deugau KV. Non-cloning amplification of specific DNA fragments from whole genomic DNA digests using DNA "indexers" . Gene. 1994, 145:163-169
217. Uskokovic M R. Kirk-Othmer Encycl Chem Technology [M]. New York: John Wiley & Sons, 1984. 41-49
218. Wada K-N et al. Codon usage tabulated from the GenBank genetic sequence data. Nucleic Acids Res. 1990. 18:2367-2411
219. Wang K et al. A simple method using T_4 DNA polymerase to clone polymerase chain reaction products. BioTechniques, 1994, 17:236-238
220. Weickert, M. J. et al. Site-directed mutagenesis of catabolite repression operator sequence in Bacillus subtilis. Proc. Natl. Acad. Sci. USA. 1990, 87:6238-6242
221. Wendland J A, Lengeler K B, Kothe E. An instant preparation method for nucleic acids of filamentous fungi [J]. Fungal Genetics Newsletter, 1996, 43:54-55
222. White BA. (ed.) Methods in Molecular Biology. Vol. 15. PCR Protocols: Current Methods and Application. Totowa, NJ: Humana, 1993
223. Witkowski JA. 50 years on Molecular Biology Hall of fame. Trends Biotechnol. 1988. 6:234
224. Wolgemuth, D.J., R. R. Behringer and M. P. Mostoller et al. 1989. Transgenic mice overexpressing the mouse hemeo-box containing gene Hox-1.4 exhibit abnormal gut development. Nature, 337:464～467
225. Wu DY. et al. The effect of temperature and oligonucleotide primer length on the specificity and efficiency of amplification by the polymerase reaction. DNA Cell Biol,1991, 10:233-238
226. Yan Xu, Dorothy Beckett. Kinetics of Biotinyl-5'-adenylate Synthesis Catalyzed by the Escherichia coli Repressor of Biotin Biosynthesis and the Stabiliby of the Enzyme-Product Complex. Biochemistry. 1994, 33: 7354-7360
227. Yanisch-Perron C. et al. Improved MB phage cloning vectors and host strain:
nucleotide sequences of the MB mp18 and PVC19 vectors. Gene. 1985, 33:103-119
228. Yonngman, P.J. et al. Construction of a cloning site near one end of Tn917 into which foreign DNA may be inserted without affecting transposition in Bacillus subtilis or expression of the transposon-borne erm gene. Plasmid. 1984, 12:1-9
229. Yoshihito I Kariyama et al. Sensitive Bioaffinity Sensor with Metastable Molecular Complex Receptor and Enzyme Amplifier. Anal. Chem. 1985, 57:496-500
230. Yoshio Komura et al. Molecular Cloning and Characterization of Two Genes for the Biotin Carboxylase and carboxyltransferase Myxococcus Xanthus. Journal of Bacteriology. 2000, 182 (19): 5462-5469
231. You-Sheng Chang, David Shiuan. Construction and Characterization of A Biotion-Regulated Gene Expression System in Escherichia coli. Applied Biochemistry and Biotechnology. 1997, 66:147-158
232. Yu L, Bloem LJ. Use of polymerase chain reaction to screen phage libraries, in ed. White B A. prococols: A Guide to Methods and Applications in Methods in Molecular Biology. Vol 15. Totowa, NJ. Humana. 1993:211-215
233. Zhen L, Swank RT. A simple and high yield method for recovering DNA from agarose gels. BioTechniqnes, 1993, 14 (6) :894-898
234. Zintz, C. B. and Beebe, D. C. Rapid re-amplification of PCR products prified form low melting point agarose gels. Biotechniques. 1991.11: 158-162
235. Zuber, P., R. Losick. Role of AbrB in SpoOA-and SpoOB-dependent Utilization of a sporulation promoter in Bacillus subtilis. J. Bacteriol. 1987, 169:2223-2230
236．安海谦等．DNA芯片技术及其应用．生物工程进展．1998，18(2)：37
237．安利国，杨桂文．基因工程技术在免疫学中的应用．生物学通报．1999，34(7)：15-17
238．A．J．哈五德主编，DNA及RNA基本实验技术，科学出版社，2002
239．曹蕾等．肿瘤的基因治疗．科学．1998，50(1)：24
240．曹先维，张鹤龄．生物素标记核酸探针的分子杂交技术及其应用．病毒杂志．1991，6(1)：1-14
241．陈永福主编．转基因动物，科学出版社，2002，86-116
242．陈章良．生物技术前程无限，知识经济，1999，(6)：22-26
243．C．W．迪芬巴赫，G．S．德维克斯勒著．PCR技术实验指南．科学出看到社，1999
244．程度，黄翔宇，李宝健．药用真菌高质量总DNA的制备及基因组文库的构建．菌物系统．2002，21(1)：137-139
245．戴旭明，李坚，傅继梁．转基因动物的研究展望．科学时报．2002年2月13日，第4版
246．董志峰，李新萍，秦松等．基因工程与海洋药物研究．海洋科学．1998，(1)：16-20
247．段海昌．征服癌症的基因疗法．科学世界．1998．(5)：46
248．段智勇，吴跃明，刘建新．生物素对高产奶牛的作用——预防蹄病和增乳饲料研究，2003，(2)：19-21
249．鄂征主编，组织培养和分子细胞学技术，北京出版，1999
250．鄂超苏，卢运玉．一种生物素快速测定方法及其结果运算的计算机程序．微生物学报．1993，33(2)：157-160
251．方桦，张依健，李玉丰等．基因工程在家禽遗传育种中的运用．广西牧兽医．2001，17(6)：41-42
252．F．奥斯伯，R．布伦特，R．E．金斯顿等著，精编分子生物学实验指南，科学出版社，1999
253．封伟贤，王振权，峞新跃．生物素缺乏及肉鸡和种鸡日粮中添加生物素效果的研究．广西农业大学学报．1995，14(2)：157-164
254．冯建文，王凤麟．高压液相色谱法测定生物素方法的探讨．饲料工业．2002，23(7)：34-35
255．郭蔼光编著．基因工程原理与技术．西北农林科技大学．2000
256．郭葆玉主编．基因工程药学．第二军医大学出版社．2000，1-23
257．贺淹才编著．简明基因工程原理．科学出版社．1998．第一版
258．J．萨姆布鲁克等著．分子克隆实验指南(第三版)．科学出版社．2002
259．李然栋，马清霞，王昕等．新型兽用疫苗的研究现状和发展动向．中国动物检疫．2002，19(11)：38-40
260．李克明，王增力．添加生物素对产蛋鸡的效果．饲料研究．1993，(3)：2-4
261．李健，候水生，黄俊纯．肉仔鸡生物素缺乏症的观测及生物素需要量的探讨．畜牧兽医学报．1994，25(4)：295-300
262．李兰．高效液相色谱电化学检测维生素预混料中生物素含量．国外畜牧学—饲料．1998，(4)：26—27
263．李青旺，武浩编著．动物繁殖学．西安地图出版社．2000
264．李育阳主编．基因表达技术．科学出版社，2002
265．梁新梅等．d-生物素代替玉米浆发酵生产谷氨酸的研究．生物技术 1996，(2)：30-34
266．刘宝全，匡春香，范圣第等．面向21世纪的基因工程．大连民族学院学报．1999．(1)1：5-12
267．刘芝．生物技术进入后基因组时代．科技潮．2000，(8)：48-49
268．刘建军，李丕武，田延军等．基因工程技术的产生、应用及研究进展．2001，(1)：12-19
269．刘国安．基因工程与外源DNA导入技术．西北师范大学学报(自然科学版)．1999，35(4)：110-112
270．刘学剑．生物素的生理动能及其应用进展．兽药与饲料添加剂．1999，4(5)：35-36
271．刘秋云，罗樨，赫然等．一种粗糙脉孢霉菌基因组DNA的快速制备方法．生物技术．2001，11(2)：38
272．陆国权．植物基因工程技术的应用与问题．世界农业．2000，(7)：36-38
273．卢圣栋编著．现代分子生物学实验技术．高等教育出版社．1993．7
274．罗云波，黄昆仑．基因工程技术的应用现状与前景．中国科技成果，2002，(2)：14-17
275．吕健，G Rakhely,KL Kovacs等．嗜热菌Aquifex Pyrophilus中Mbh2基因簇的鉴定和部分基因的克隆及测序．微生物学报．2001，41(6)：674-679
276．马翠然，李素霞．种鸡缺生物素对孵化成绩的影响．家禽与禽病防治．1999，(8)：33
277．马大龙主编．生物技术药物．科学出版社．2001
278．彭秀玲，袁汉英，谢毅等编著．基因工程实验技术(第二版)．湖南科学技术出版社．1998
279．钱建飞，钟声．基因工程技术在畜牧兽医上的应用及展望．畜牧与兽医．1999，31(1)：41-44
280．乔建军，杜连祥．一种快速有效的枯草芽孢杆菌染色体的提取方法．生物技术．2001，11(2)：38-40
281．秦鹏春等编著．哺乳动物胚胎学．科学出版社．2001
282．瞿礼嘉，顾红雅，胡苹，陈章良编著．现代生物技术导论，高等教育出版社．1998
283．曲殿波，刘传暄，张艳红等．O_(139)霍乱弧菌质粒基因组文库的建立及O-抗原基因的筛选．微生物学报．2001，41(1)：65-69
284．沈同，王镜岩主编．生物化学(上、下册)．高等教育出版社．1991，第二版
285．盛自华．纯生物素的检测方法．发酵科技通讯．1998，72(2)：6-7，39
286．石磊，杨晓莉，王国栋等．食物和饲料中生物素的测定方法，营养学报．2002，24(2)：181—184
287．宋礼华，桂向东，徐键等．一个新的经济增长点：生物医药产业的现状和发展趋势．生物学杂志．2000，15(5)：27-30
288．孙树汉．基因工程原理与方法．人民军医出版社，2001，9-15
289．孙乃恩，孙东旭，朱德煦编著．分子遗传学．南京大学出版社．2001，470-487
290．唐冬生，夏家辉．新型基因工程药物．生命科学研究．1999，3(2)：92-95
291．唐清．大鼠AKPD基因的分子克隆研究Ⅰ．大鼠基因组文库的构建．西南民族学院学报．自然科学版．1998，24(1)：42-47
292．童克中著．基因及其表达．科学出版社，2001，274-276
293．吴瑞娟．基因工程在农业和医学上的应用．生物学通报．2000，37(4)：30-31
294．汪富泉．分子生物学与基因工程引发的思考．世界科技研究与发展．2000，22(4)：45-49
295．王保莉，巩普遍编写．生物制品概论．西北农林科技大学．2002
296．王福荣，俞津婷．生物素测定方法的研究(第Ⅰ报)．中国酿造．1992，(4)：14-18
297．王福荣，张琳，俞津婷．生物素测定方法的研究(第Ⅱ报)．中国酿造．1994，(1)：17-19
298．王福荣，俞津婷，张琳．利用异硫氰酸荧光素标记亲合素荧光法测定生物素含量．氨基酸杂志．1994，(3)：47-49
299．王和民，齐广海主编．维生素营养研究进展，中国科学技术出版社，1993
300．王军志主编．生物技术药物研究开发和质量控制．科学出版社，2002，3-74
301．王胜林．饲料添加生物素和维生素E能改善猪肉品质．兽药与饲料添加剂，2000，5(5)：28
302．王延庆，徐瑾，项坤三等．应用光敏生物素标记探针进行分子杂交的技术．中华医学遗传学杂志，1993，10(2)：104-106
303．汪永庆，王新国，徐来祥等．一种动物基因组DNA提取方法的改进．动物学杂志．2001，36(1)：27-29
304．王友明．饲料中营养物质对猪肉品质的影响．饲料研究，2000，(8)：17-18，20
305．吴乃虎编著．基因工程原理(上册)．科学出版社，2000
306．吴乃虎编著．基因工程原理(下册)．科学出版社，2001
307．伍新尧，罗超权，马涧泉主编．分子遗传学与基因工程．河南医科大学出版社．1997
308．吴冠芸，潘华珍，吴晕主编．生物化学与分子生物学实验常用数据手册．科学出版社，1999
309．吴梧桐主编．现代生化药学，中国医药科技出版社，2002
310．武英，王敬华，赵燕等．生物素对产蛋鸡生产性能的影响．中国饲料，1995，(21)：19-20
311．谢平，宋惠萍．基因工程的发展及医学意义．医学与社会，2000，(4)：3-5
312．谢庆阁．根除畜禽传染病的新对策——动物基因工程抗病育种．生物工程进展．1992，12(2)：30-33，43
313．熊辛，鄂征．生物素标记检测在基因探查中的应用．细胞生物学杂志，1990，12(4)：183-186
314．许崇任，虞建军．转基因产业的产生和发展．饲料广角．2000，(16)：10-11
315．徐幼平，陈正贤，吴建祥等．微生物发酵液中生物素含量的ELISA测定．微生物
学通报．2000，27(1)：47-50
316．徐阳．面向未来的生物技术．科学世界．1998，(3)：32
317．徐士清．基因工程与21世纪养猪业．浙江农业科学．2002，(4)：202-203
318．阎隆飞，张玉麟主编．分子生物学(第二版)．中国农业大学出版社．1997
319．严宝霞．基因与药学发展．中国医药导刊．2001，3(4)：270-273
320．严云勤，李光鹏，郑小民编著．发育生物学原理与胚胎工程．黑龙江科学技术出版社．1995
321．杨凤主编．动物营养学．中国农业出版社，1993，86
322．杨红文等，d，1-2，3，4，6-四氢-2-氧-1氢噻吩并[3，4-d]咪唑-4-戊酸的合成，化学通报，2000，(8)：34
323．杨红．用ELISA法测定基因转殖酵母菌发酵液中生物素．中国药师，2002，5(6)：351-353
324．杨吉成，缪竞诚等编著．医学基因工程．化学工业出版社，2003，16-19
325．于德强，张岚．重组药物工艺经济分析．中国生物工程杂志．2003，23(3)：85-89
326．余克伦，罗延荣．生物素标记核酸探针的应用概况，中国兽医科技．1990，(2)：17-18
327．俞键．基因工程进展与二十一世纪人类生活．天津科技．2002，29(3)：48-50
328．张惠展著．基因工程概论．华东理工大学出版社，2000
329．张明峰．动植物转基因技术育种的成就．世界农业．2000，(4)：42-43
330．张树庸．我国基因工程研究概况．实验动物科学与管理．2001，18(4)：30-33
331．张伟，周桂莲．母猪的维生素营养．养猪．2001，(1)：5-8
332．张学敏，王宜强主编．靶向新基因的分子克隆策略——理论与方法．军事医学科学出版社．1999
333．周林．生物素和维生素E对肉鸡屠宰性能和肉品质的影响．饲料博览．2000，(8)：6-7
334．周桂莲．生物素在畜禽生产中的作用．中国饲料．2000，(6)：14-15
335．祖荫光，周利．谷氨酸发酵中生物素含量的测定．发酵科技通讯．2003，32(2)：18-19
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