title: Characterization of thermolide biosynthetic genes and a new thermolide from sister thermophilic fungi.
abstract: Prior chemical analysis of obligate thermophilic fungus Talaromyces thermophilus led to the discovery of thermolides A-F, 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' mixed polyketide/amino acid structure encodes a hybrid polyketide synthase-nonribosomal peptide synthetase (PKS-NRPS). Our results reveal the first fungal hybrid iterative PKS-NRPS 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-NRPS hybrids.
authors.affiliation: Texas Therapeutics Institute, the Brown Foundation Institute of Molecular Medicine, the University of Texas Health Science Center at Houston , Houston, Texas 77054, United States.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Niu
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.forename: Qun
authors.initials: Q
authors.lastname: Yue
authors.forename: Baile
authors.initials: B
authors.lastname: Wang
authors.forename: Junxian
authors.initials: J
authors.lastname: Zhang
authors.forename: Chunyan
authors.initials: C
authors.lastname: Zhu
authors.forename: Keqin
authors.initials: K
authors.lastname: Zhang
authors.forename: Gerald F
authors.initials: GF
authors.lastname: Bills
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: An
mesh_terms: D001203:Ascomycota / Q000235:genetics / Q000378:metabolism*; D007769:Lactams / Q000737:chemistry; D047029:Lactams, Macrocyclic / Q000737:chemistry / Q000302:isolation & purification*; D015394:Molecular Structure; D010453:Peptide Synthases / Q000378:metabolism*; D048630:Polyketide Synthases / Q000378:metabolism*; D032901:Talaromyces / Q000235:genetics / Q000378:metabolism
chemical_list: D007769:Lactams; D047029:Lactams, Macrocyclic; D048630:Polyketide Synthases; D010453:Peptide Synthases; C104385:non-ribosomal peptide synthase