title: Type III polyketide synthase beta-ketoacyl-ACP starter unit and ethylmalonyl-CoA extender unit selectivity discovered by Streptomyces coelicolor genome mining.
abstract: Polyketide synthases (PKSs) are involved in the biosynthesis of many important natural products. In bacteria, type III PKSs typically catalyze iterative decarboxylation and condensation reactions of malonyl-CoA building blocks in the biosynthesis of polyhydroxyaromatic products. Here it is shown that Gcs, a type III PKS encoded by the sco7221 ORF of the bacterium Streptomyces coelicolor, is required for biosynthesis of the germicidin family of 3,6-dialkyl-4-hydroxypyran-2-one natural products. Evidence consistent with Gcs-catalyzed elongation of specific beta-ketoacyl-ACP products of the fatty acid synthase FabH with ethyl- or methylmalonyl-CoA in the biosynthesis of germicidins is presented. Selectivity for beta-ketoacyl-ACP starter units and ethylmalonyl-CoA as an extender unit is unprecedented for type III PKSs, suggesting these enzymes may be capable of utilizing a far wider range of starter and extender units for natural product assembly than believed until now.
authors.affiliation: Department of Chemistry, University of Warwick, Coventry CV4 7AL, U.K
authors.forename: Lijiang
authors.initials: L
authors.lastname: Song
authors.forename: Francisco
authors.initials: F
authors.lastname: Barona-Gomez
authors.forename: Christophe
authors.initials: C
authors.lastname: Corre
authors.forename: Longkuan
authors.initials: L
authors.lastname: Xiang
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Udwary
authors.forename: Michael B
authors.initials: MB
authors.lastname: Austin
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Noel
authors.forename: Bradley S
authors.initials: BS
authors.lastname: Moore
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Challis
mesh_terms: D015099:3-Oxoacyl-(Acyl-Carrier-Protein) Synthase / Q000378:metabolism*; D000214:Acyl Coenzyme A / Q000378:metabolism*; D000429:Alcohol Oxidoreductases / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D016680:Genome, Bacterial; D007527:Isoenzymes / Q000378:metabolism*; D019906:Nuclear Magnetic Resonance, Biomolecular; D048372:Streptomyces coelicolor / Q000235:genetics*
chemical_list: D000214:Acyl Coenzyme A; D001426:Bacterial Proteins; D007527:Isoenzymes; C102829:ethylmalonyl-coenzyme A; D000429:Alcohol Oxidoreductases; C087192:polyketide synthase ketoreductase; C078182:beta-ketoacyl-acyl carrier protein synthase I; D015099:3-Oxoacyl-(Acyl-Carrier-Protein) Synthase