Stereospecific acyl transfers on the erythromycin-producing polyketide synthase.
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.
Marsden
A F
AF
Cambridge Centre for Molecular Recognition, University of Cambridge, United Kingdom.
Caffrey
P
P
Aparicio
J F
JF
Loughran
M S
MS
Staunton
J
J
Leadlay
P F
PF
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
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