Stereospecific Acyl Transfers on the Erythromycin-Producing Polyketide Synthase
- 21 January 1994
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 263 (5145) , 378-380
- https://doi.org/10.1126/science.8278811
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.Keywords
This publication has 21 references indexed in Scilit:
- Heterologous expression in Escherichia coli of an intact multienzyme component of the erythromycin‐producing polyketide synthaseEuropean Journal of Biochemistry, 1993
- Identification of DEBS 1, DEBS 2 and DEBS 3, the multienzyme polypeptides of the erythromycin‐producing polyketide synthase from Saccharopolyspora erythraeaFEBS Letters, 1992
- The Extraordinary Enzymes Involved in Erythromycin BiosynthesisAngewandte Chemie International Edition in English, 1991
- Fatty acid synthase, a proficient multifunctional enzymeBiochemistry, 1989
- The polyether and macrolide antibiotics: biogenetic analysis and structural correlationsNatural Product Reports, 1989
- Macrolide biosynthesis. Tylactone formation involves the processive addition of three carbon unitsJournal of the American Chemical Society, 1987
- Biosynthesis of lasalocid A: biochemical mechanism for assembly of the carbon frameworkBiochemistry, 1986
- Unified stereochemical model of polyether antibiotic structure and biogenesisJournal of the American Chemical Society, 1983
- The Biosynthesis of Long-Chain Fatty Acids. Incorporation of Radioactivity from Stereospecifically Tritiated Malonyl Thiol Esters, and the Stereochemistry of the Acetyl-CoA Carboxylase ReactionEuropean Journal of Biochemistry, 1977
- Macrolide Stereochemistry. III. A Configurational Model for Macrolide Antibiotics1Journal of the American Chemical Society, 1965