文摘
Prior chemical analysis of obligate thermophilic fungus Talaromyces thermophilus led to the discovery of thermolides A鈥揊, six previously undescribed members of the lactam-bearing macrolactone class. A combination of chemical screening, genome analyses, and genetic manipulation led to the identification of the thermolide biosynthetic genes from sister thermophilic fungi T. thermophilus and Thermomyces lanuginosus and a new thermolide. The biosynthetic locus for the thermolides鈥?mixed polyketide/amino acid structure encodes a hybrid polyketide synthase鈥搉onribosomal peptide synthetase (PKS鈥揘RPS). Our results reveal the first fungal hybrid iterative PKS鈥揘RPS genes involved in the biosynthesis of bacterial-like hybrid macrolactones instead of typical fungal tetramic acids-containing metabolites. The finding provides an insight into the convergent biosynthetic end products that bridge the gap between the modular and iterative PKS鈥揘RPS hybrids.