title: Collaborative Biosynthesis of Maleimide- and Succinimide-Containing Natural Products by Fungal Polyketide Megasynthases.
abstract: Fungal polyketide synthases (PKSs) can function collaboratively to synthesize natural products of significant structural diversity. Here we present a new mode of collaboration between a highly reducing PKS (HRPKS) and a PKS-nonribosomal peptide synthetase (PKS-NRPS) in the synthesis of oxaleimides from the Penicillium species. The HRPKS is recruited in the synthesis of an olefin-containing free amino acid, which is activated and incorporated by the adenylation domain of the PKS-NRPS. The precisely positioned olefin from the unnatural amino acid is proposed to facilitate a scaffold rearrangement of the PKS-NRPS product to forge the maleimide and succinimide cores of oxaleimides.
authors.affiliation: Department of Pharmaceutical Sciences, University of Shizuoka , Shizuoka 422-8526, Japan.
authors.forename: Michio
authors.initials: M
authors.lastname: Sato
authors.forename: Jacob E
authors.initials: JE
authors.lastname: Dander
authors.forename: Chizuru
authors.initials: C
authors.lastname: Sato
authors.forename: Yiu-Sun
authors.initials: YS
authors.lastname: Hung
authors.forename: Shu-Shan
authors.initials: SS
authors.lastname: Gao
authors.forename: Man-Cheng
authors.initials: MC
authors.lastname: Tang
authors.forename: Leibniz
authors.initials: L
authors.lastname: Hang
authors.affiliation: Medicinal Chemistry Department, University of Utah , Salt Lake City, Utah 84112, United States.
authors.forename: Jaclyn M
authors.initials: JM
authors.lastname: Winter
authors.forename: Neil K
authors.identifier: 0000-0002-7793-2629
authors.initials: NK
authors.lastname: Garg
authors.affiliation: Department of Pharmaceutical Sciences, University of Shizuoka , Shizuoka 422-8526, Japan.
authors.forename: Kenji
authors.identifier: 0000-0002-0463-4831
authors.initials: K
authors.lastname: Watanabe
authors.forename: Yi
authors.identifier: 0000-0003-1597-0141
authors.initials: Y
authors.lastname: Tang
mesh_terms: D001688:Biological Products / Q000737:chemistry / Q000378:metabolism*; D008301:Maleimides / Q000737:chemistry / Q000378:metabolism*; D008968:Molecular Conformation; D010407:Penicillium / Q000201:enzymology*; D048630:Polyketide Synthases / Q000737:chemistry / Q000378:metabolism*; D013388:Succinimides / Q000737:chemistry / Q000378:metabolism*
chemical_list: D001688:Biological Products; D008301:Maleimides; D013388:Succinimides; C032620:succinimide; C043592:maleimide; D048630:Polyketide Synthases