title: Supramolecular templating in kirromycin biosynthesis: the acyltransferase KirCII loads ethylmalonyl-CoA extender onto a specific ACP of the trans-AT PKS.
abstract: In the biosynthesis of complex polyketides, acyltransferase domains (ATs) are key determinants of structural diversity. Their specificity and position in polyketide synthases (PKSs) usually controls the location and structure of building blocks in polyketides. Many bioactive polyketides, however, are generated by trans-AT PKSs lacking internal AT domains. They were previously believed to use mainly malonyl-specific free-standing ATs. Here, we report a mechanism of structural diversification, in which the trans-AT KirCII regiospecifically incorporates the unusual extender unit ethylmalonyl-CoA in kirromycin polyketide biosynthesis.
authors.affiliation: Eberhard-Karls-Universität Tübingen, Interfakultäres Institut für Mikrobiologie und Infektionsmedizin, Mikrobiologie/Biotechnologie, 72076 Tübingen, Germany.
authors.forename: Ewa M
authors.initials: EM
authors.lastname: Musiol
authors.forename: Thomas
authors.initials: T
authors.lastname: Härtner
authors.forename: Andreas
authors.initials: A
authors.lastname: Kulik
authors.forename: Jana
authors.initials: J
authors.lastname: Moldenhauer
authors.forename: Jörn
authors.initials: J
authors.lastname: Piel
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wohlleben
authors.forename: Tilmann
authors.initials: T
authors.lastname: Weber
mesh_terms: D000213:Acyl Carrier Protein / Q000378:metabolism*; D000214:Acyl Coenzyme A / Q000737:chemistry* / Q000378:metabolism*; D000217:Acyltransferases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D000900:Anti-Bacterial Agents / Q000096:biosynthesis; D048630:Polyketide Synthases / Q000737:chemistry / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011728:Pyridones / Q000378:metabolism; D013237:Stereoisomerism; D013302:Streptomyces / Q000235:genetics / Q000378:metabolism; D013379:Substrate Specificity
chemical_list: D000213:Acyl Carrier Protein; D000214:Acyl Coenzyme A; D000900:Anti-Bacterial Agents; D011728:Pyridones; C102829:ethylmalonyl-coenzyme A; D048630:Polyketide Synthases; D000217:Acyltransferases; C008536:mocimycin