title: Streptomyces coelicolor RedP and FabH enzymes, initiating undecylprodiginine and fatty acid biosynthesis, exhibit distinct acyl-CoA and malonyl-acyl carrier protein substrate specificities.
abstract: RedP is proposed to initiate undecylprodiginine biosynthesis in Streptomyces coelicolor by condensing an acyl-CoA with malonyl-ACP and is homologous to FabH that catalyzes the same reaction for initiation of fatty acid biosynthesis. Herein, we report the substrate specificities of RedP and FabH from assays using pairings of two acyl-CoA substrates (acetyl-CoA and isobutyryl-CoA) and two malonyl-ACP substrates (malonyl-RedQ and malonyl-FabC). RedP activity was observed only with a pairing of acetyl-CoA and malonyl-RedQ, consistent with its proposed role in initiating the formation of acetyl-CoA-derived prodiginines. Malonyl-FabC is not a substrate for RedP, indicating that ACP specificity is one of the factors that permit a separation between prodiginine and fatty acid biosynthetic processes. FabH demonstrated greater catalytic efficiency for isobutyryl-CoA in comparison with acetyl-CoA using malonyl-FabC, consistent with the observation that in streptomycetes, a broad mixture of fatty acids is synthesized, with those derived from branched-chain acyl-CoA starter units predominating. Diminished FabH activity was also observed using malonyl-RedQ with the same preference for isobutyryl-CoA, completing biochemical and genetic evidence that in the absence of RedP this enzyme can produce branched-chain alkyl prodiginines.
authors.affiliation: Department of Chemistry, Portland State University, Portland, OR, USA.
authors.forename: Renu
authors.initials: R
authors.lastname: Singh
authors.forename: SangJoon
authors.initials: S
authors.lastname: Mo
authors.forename: Galina
authors.initials: G
authors.lastname: Florova
authors.forename: Kevin A
authors.initials: KA
authors.lastname: Reynolds
mesh_terms: D000213:Acyl Carrier Protein / Q000378:metabolism*; D000214:Acyl Coenzyme A / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D005227:Fatty Acids / Q000096:biosynthesis*; D011353:Prodigiosin / Q000031:analogs & derivatives* / Q000096:biosynthesis; D048372:Streptomyces coelicolor / Q000201:enzymology*; D013379:Substrate Specificity
chemical_list: D000213:Acyl Carrier Protein; D000214:Acyl Coenzyme A; D001426:Bacterial Proteins; D005227:Fatty Acids; C528938:undecylprodiginine; C050106:isobutyryl-coenzyme A; D011353:Prodigiosin