title: Stereospecific acyl transfers on the erythromycin-producing polyketide synthase.
abstract: During assembly of complex polyketide antibiotics like erythromycin A, molecular recognition by the multienzyme polyketide synthase controls the stereochemical outcome as each successive methylmalonyl-coenzyme A (CoA) extender unit is added. Acylation of the purified erythromycin-producing polyketide synthase has shown that all six acyltransferase domains have identical stereospecificity for their normal substrate, (2S)-methylmalonyl-CoA. In contrast, the configuration of the methyl-branched centers in the product, that are derived from (2S)-methylmalonyl-CoA, is different. Stereoselection during the chain building process must, therefore, involve additional epimerization steps.
authors.affiliation: Cambridge Centre for Molecular Recognition, University of Cambridge, United Kingdom.
authors.forename: A F
authors.initials: AF
authors.lastname: Marsden
authors.forename: P
authors.initials: P
authors.lastname: Caffrey
authors.forename: J F
authors.initials: JF
authors.lastname: Aparicio
authors.forename: M S
authors.initials: MS
authors.lastname: Loughran
authors.forename: J
authors.initials: J
authors.lastname: Staunton
authors.forename: P F
authors.initials: PF
authors.lastname: Leadlay
mesh_terms: D000105:Acetyl Coenzyme A / Q000378:metabolism; D000214:Acyl Coenzyme A / Q000378:metabolism*; D004917:Erythromycin / Q000096:biosynthesis*; D008316:Malonyl Coenzyme A / Q000378:metabolism; D008968:Molecular Conformation; D009097:Multienzyme Complexes / Q000737:chemistry / Q000378:metabolism*; D019998:Racemases and Epimerases / Q000378:metabolism; D016930:Saccharopolyspora / Q000201:enzymology; D013237:Stereoisomerism; D013379:Substrate Specificity
chemical_list: D000214:Acyl Coenzyme A; D009097:Multienzyme Complexes; C015357:methylmalonyl-coenzyme A; C009061:propionyl-coenzyme A; D008316:Malonyl Coenzyme A; D004917:Erythromycin; D000105:Acetyl Coenzyme A; D019998:Racemases and Epimerases; C021581:methylmalonyl-coenzyme A racemase