title: Enzymatic synthesis of dilactone scaffold of antimycins.
abstract: Antimycins are a family of natural products possessing outstanding biological activities and unique structures, which have intrigued chemists for over a half century. The antimycin structural skeleton is built on a nine-membered dilactone ring containing one alkyl, one acyloxy, two methyl moieties, and an amide linkage connecting to a 3-formamidosalicylic acid. Although a biosynthetic gene cluster for antimycins was recently identified, the enzymatic logic that governs the synthesis of antimycins has not yet been revealed. In this work, the biosynthetic pathway for antimycins was dissected by both genetic and enzymatic studies for the first time. A minimum set of enzymes needed for generation of the antimycin dilactone scaffold were identified, featuring a hybrid nonribosomal peptide synthetase (NRPS)-polyketide synthase (PKS) assembly line containing both cis- and trans-acting components. Several antimycin analogues were further produced using in vitro enzymatic total synthesis based on the substrate promiscuity of this NRPS-PKS machinery.
authors.affiliation: Department of Chemical and Biomolecular Engineering and Energy Biosciences Institute, University of California, Berkeley, CA 94720, USA.
authors.forename: Moriah
authors.initials: M
authors.lastname: Sandy
authors.forename: Zhe
authors.initials: Z
authors.lastname: Rui
authors.forename: Joe
authors.initials: J
authors.lastname: Gallagher
authors.forename: Wenjun
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000595:Amino Acid Sequence; D000968:Antimycin A / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D002853:Chromatography, Liquid; D007783:Lactones / Q000737:chemistry*; D013058:Mass Spectrometry; D048630:Polyketide Synthases / Q000737:chemistry*
chemical_list: D007783:Lactones; C032456:antimycin; D000968:Antimycin A; D048630:Polyketide Synthases