title: Polyketide synthase chimeras reveal key role of ketosynthase domain in chain branching.
abstract: Biosynthesis of rhizoxin in Burkholderia rhizoxinica affords an unusual polyketide synthase module with ketosynthase and branching domains that install the δ-lactone, conferring antimitotic activity. To investigate their functions in chain branching, we designed chimeric modules with structurally similar domains from a glutarimide-forming module and a dehydratase. Biochemical, kinetic and mutational analyses reveal a structural role of the accessory domains and multifarious catalytic actions of the ketosynthase.
authors.affiliation: Department of Biomolecular Chemistry, Leibniz Institute for Natural Product Research and Infection Biology (HKI), Jena, Germany.
authors.forename: Srividhya
authors.initials: S
authors.lastname: Sundaram
authors.affiliation: Department of Biomolecular Chemistry, Leibniz Institute for Natural Product Research and Infection Biology (HKI), Jena, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Heine
authors.affiliation: Department of Biomolecular Chemistry, Leibniz Institute for Natural Product Research and Infection Biology (HKI), Jena, Germany.|Chair of Natural Product Chemistry, Friedrich Schiller University, Jena, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Hertweck
mesh_terms: D000217:Acyltransferases / Q000737:chemistry / Q000378:metabolism*; D019117:Burkholderia / Q000201:enzymology* / Q000378:metabolism; D018942:Macrolides / Q000737:chemistry / Q000378:metabolism; D008968:Molecular Conformation; D048630:Polyketide Synthases / Q000737:chemistry / Q000378:metabolism*; D061065:Polyketides / Q000737:chemistry / Q000378:metabolism
chemical_list: D018942:Macrolides; D061065:Polyketides; D048630:Polyketide Synthases; C041443:rhizoxin; D000217:Acyltransferases