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Polyketide decarboxylative chain termination preceded by O-sulfonation in curacin A biosynthesis

Gu, L and Wang, B and Kulkarni, A and Gehret, JJ and Lloyd, KR and Gerwick, L and Gerwick, WH and Wipf, P and Håkansson, K and Smith, JL and Sherman, DH (2009) Polyketide decarboxylative chain termination preceded by O-sulfonation in curacin A biosynthesis. Journal of the American Chemical Society, 131 (44). 16033 - 16035. ISSN 0002-7863

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Abstract

(Figure Presented) Biosynthetic innovation in natural product systems is driven by the recruitment of new genes and enzymes into these complex pathways. Here, an unprecedented decarboxylative chain termination mechanism is described for the polyketide synthase of curacin A, an anticancer lead compound isolated from the marine cyanobacterium Lyngbya majuscula. The unusual chain termination module containing adjacent sulfotransferase (ST) and thioesterase (TE) catalytic domains embedded in CurM was biochemically characterized. The TE was proved to catalyze a hydrolytic chain release of the polyketide chain elongation intermediate. Moreover, a selective ST-mediated sulfonation of the (R)-β-hydroxyl group was found to precede TE-mediated hydrolysis, triggering a successive decarboxylative elimination and resulting in the formation of a rare terminal olefin in the final metabolite. Copyright © 2009 American Chemical Society.

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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Gu, L
Wang, B
Kulkarni, A
Gehret, JJ
Lloyd, KR
Gerwick, L
Gerwick, WH
Wipf, Ppwipf@pitt.eduPWIPF
Håkansson, K
Smith, JL
Sherman, DH
Date: 27 November 2009
Date Type: Publication
Journal or Publication Title: Journal of the American Chemical Society
Volume: 131
Number: 44
Page Range: 16033 - 16035
DOI or Unique Handle: 10.1021/ja9071578
Schools and Programs: Dietrich School of Arts and Sciences > Chemistry
Refereed: Yes
ISSN: 0002-7863
MeSH Headings: Antineoplastic Agents; Bacterial Proteins; Cyanobacteria; Cyclopropanes--metabolism; Decarboxylation; Macrolides--metabolism; Metabolic Networks and Pathways; Polyketide Synthases--metabolism; Sulfones; Sulfotransferases; Thiazoles--metabolism; Tubulin Modulators
Other ID: NLM NIHMS183561, NLM PMC2839324
PubMed Central ID: PMC2839324
PubMed ID: 19835378
Date Deposited: 07 Jun 2013 20:04
Last Modified: 02 Feb 2019 16:56
URI: http://d-scholarship.pitt.edu/id/eprint/18844

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