Metabolic coupling of dehydration and decarboxylation in the curacin A pathway: functional identification of a mechanistically diverse enzyme pair.

Abstract

This study describes the functional identification of a pair of mechanistically diverse enzymes that catalyze the successive dehydration (CurE ECH1) and decarboxylation (CurF ECH2) of (S)-HMG-ACP to generate a 3-methylcrotonyl-ACP intermediate, the presumed precursor of the cyclopropyl ring in curacin A. The reactions catalyzed by ECH1 and ECH2 are found in a broad cross-section of microbial natural product gene clusters and participate in the introduction of carbon chain branch points and functional group diversity as key steps in the HMG-CoA synthase mediated addition of C-2 from acetate to the beta-carbonyl group of polyketide chains.

• Authors: Liangcai Gu, Junyong Jia, Haichuan Liu, Kristina Håkansson, William H Gerwick, David H Sherman
• Journal: Journal of the American Chemical Society (J Am Chem Soc) Vol. 128 Issue 28 Pg. 9014-5 (Jul 19 2006) ISSN: 0002-7863 [Print] United States
• PMID: 16834357 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Bacterial Proteins
• Cyclopropanes
• Enzymes
• Thiazoles
• curacin A

Topics

• Bacterial Proteins (chemistry, metabolism)
• Cyanobacteria (enzymology)
• Cyclopropanes (chemistry, metabolism)
• Enzymes (chemistry, metabolism)
• Molecular Structure
• Thiazoles (chemistry, metabolism)