title: A fungal ketoreductase domain that displays substrate-dependent stereospecificity.
abstract: Iterative highly reducing polyketide synthases from filamentous fungi are the most complex and enigmatic type of polyketide synthase discovered to date. Here we uncover an unusual degree of programming by the hypothemycin highly reducing polyketide synthase, in which a single ketoreductase domain shows stereospecificity that is controlled by substrate length. Mapping of the structural domains responsible for this feature allowed for the biosynthesis of an unnatural diastereomer of the natural product dehydrozearalenol.
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of California-Los Angeles, Los Angeles, California, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhou
authors.forename: Zhizeng
authors.initials: Z
authors.lastname: Gao
authors.forename: Kangjian
authors.initials: K
authors.lastname: Qiao
authors.forename: Jingjing
authors.initials: J
authors.lastname: Wang
authors.forename: John C
authors.initials: JC
authors.lastname: Vederas
authors.forename: Yi
authors.initials: Y
authors.lastname: Tang
mesh_terms: D000595:Amino Acid Sequence; D005656:Fungal Proteins / Q000737:chemistry / Q000378:metabolism; D005658:Fungi / Q000201:enzymology; D008969:Molecular Sequence Data; D009249:NADP / Q000378:metabolism; D048630:Polyketide Synthases / Q000737:chemistry* / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013237:Stereoisomerism; D013379:Substrate Specificity; D015025:Zearalenone / Q000031:analogs & derivatives; D015029:Zeranol / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism
chemical_list: D005656:Fungal Proteins; D011994:Recombinant Proteins; C120440:hypothemycin; D009249:NADP; D015025:Zearalenone; D015029:Zeranol; D048630:Polyketide Synthases