title: Biosynthesis of antimycins with a reconstituted 3-formamidosalicylate pharmacophore in Escherichia coli.
abstract: Antimycins are a family of natural products generated from a hybrid nonribosomal peptide synthetase (NRPS)-polyketide synthase (PKS) assembly line. Although they possess an array of useful biological activities, their structural complexity makes chemical synthesis challenging, and their biosynthesis has thus far been dependent on slow-growing source organisms. Here, we reconstituted the biosynthesis of antimycins in Escherichia coli, a versatile host that is robust and easy to manipulate genetically. Along with Streptomyces genetic studies, the heterologous expression of different combinations of ant genes enabled us to systematically confirm the functions of the modification enzymes, AntHIJKL and AntO, in the biosynthesis of the 3-formamidosalicylate pharmacophore of antimycins. Our E. coli-based antimycin production system can not only be used to engineer the increased production of these bioactive compounds, but it also paves the way for the facile generation of novel and diverse antimycin analogues through combinatorial biosynthesis.
authors.forename: Joyce
authors.initials: J
authors.lastname: Liu
authors.forename: Xuejun
authors.initials: X
authors.lastname: Zhu
authors.affiliation: ∥School of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT, United Kingdom.
authors.forename: Ryan F
authors.initials: RF
authors.lastname: Seipke
authors.forename: Wenjun
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000968:Antimycin A / Q000031:analogs & derivatives* / Q000096:biosynthesis; D001688:Biological Products / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism; D005798:Genes, Bacterial / Q000235:genetics; D012459:Salicylates / Q000378:metabolism*; D013302:Streptomyces / Q000235:genetics
chemical_list: D001688:Biological Products; D012459:Salicylates; C032456:antimycin; D000968:Antimycin A
keywords: 3-formamidosalicylate; antimycin biosynthesis; formyltransferase; heterologous expression; multicomponent oxygenase; nonribosomal peptide/polyketide hybrid