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Science 21 January 1994:
Vol. 263. no. 5145, pp. 378 - 380
DOI: 10.1126/science.8278811
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Articles

Science, Vol 263, Issue 5145, 378-380
Copyright © 1994 by American Association for the Advancement of Science

articles

Stereospecific acyl transfers on the erythromycin-producing polyketide synthase

AF Marsden, P Caffrey, JF Aparicio, MS Loughran, J Staunton, and PF Leadlay

Cambridge Centre for Molecular Recognition, University of Cambridge, United Kingdom.

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.


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