Type III polyketide synthase beta-ketoacyl-ACP starter unit and ethylmalonyl-CoA extender unit selectivity discovered by Streptomyces coelicolor genome mining.
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.
Song
Lijiang
L
Department of Chemistry, University of Warwick, Coventry CV4 7AL, U.K
Barona-Gomez
Francisco
F
Corre
Christophe
C
Xiang
Longkuan
L
Udwary
Daniel W
DW
Austin
Michael B
MB
Noel
Joseph P
JP
Moore
Bradley S
BS
Challis
Gregory L
GL
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*
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