Polyketide Decarboxylative Chain Termination Preceded by O-Sulfonation in Curacin A Biosynthesis

被引：75

作者：

Gu, Liangcai ^{[1
,2
]}

Wang, Bo ^{[1
,2
]}

Kulkarni, Amol ^{[3
]}

Gehret, Jennifer J. ^{[1
,2
]}

Lloyd, Kayla R. ^{[3
]}

Gerwick, Lena ^{[4
]}

Gerwick, William H. ^{[4
]}

Wipf, Peter ^{[3
]}

Hakansson, Kristina ^{[1
,2
]}

Smith, Janet. L. ^{[1
,2
]}

Sherman, David H. ^{[1
,2
]}

机构：

[1] Univ Michigan, Inst Life Sci, Dept Biochem Med, Dept Chem,Dept Biol Chem, Ann Arbor, MI 48109 USA

[2] Univ Michigan, Dept Microbiol & Immunol, Ann Arbor, MI 48109 USA

[3] Univ Pittsburgh, Dept Chem, Pittsburgh, PA 15260 USA

[4] Univ Calif San Diego, Scripps Inst Oceanog, La Jolla, CA 92093 USA

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2009年 / 131卷 / 44期

关键词：

NONRIBOSOMAL PEPTIDE ANTIBIOTICS; GENE-CLUSTER; NATURAL-PRODUCT; PATHWAY; VERSATILITY; MACHINERY; LOGIC;

D O I：

10.1021/ja9071578

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

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)-beta-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.

引用

页码：16033 / +

页数：5

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