Biosynthesis of sphinganine-analog mycotoxins

被引：33

作者：

Du, L. ^{[1
]}

Zhu, X. ^{[1
]}

Gerber, R. ^{[1
]}

Huffman, J. ^{[1
]}

Lou, L. ^{[1
]}

Jorgenson, J. ^{[1
]}

Yu, F. ^{[1
]}

Zaleta-Rivera, K. ^{[1
]}

Wang, Q. ^{[2
]}

机构：

[1] Univ Nebraska, Dept Chem, Lincoln, NE 68588 USA

[2] Zhejiang Univ, Dept Hort, Hangzhou 310029, Peoples R China

来源：

JOURNAL OF INDUSTRIAL MICROBIOLOGY & BIOTECHNOLOGY | 2008年 / 35卷 / 06期

关键词：

biosynthesis; sphinganine-analog mycotoxins; polyketides; fumonisins; AAL-toxins;

D O I：

10.1007/s10295-008-0316-y

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

Sphinganine-analog mycotoxins (SAMT) are polyketide-derived natural products produced by a number of plant pathogenic fungi and are among the most economically important mycotoxins. The toxins are structurally similar to sphinganine, a key intermediate in the biosynthesis of ceramides and sphingolipids, and competitive inhibitors for ceramide synthase. The inhibition of ceramide and sphingolipid biosynthesis is associated with several fatal diseases in domestic animals and esophageal cancer and neural tube defects in humans. SAMT contains a highly reduced, acyclic polyketide carbon backbone, which is assembled by a single module polyketide synthase. The biosynthesis of SAMT involves a unique polyketide chain-releasing mechanism, in which a pyridoxal 5'-phosphate-dependent enzyme catalyzes the termination, offloading and elongation of the polyketide chain. This leads to the introduction of a new carbon-carbon bond and an amino group to the polyketide chain. The mechanism is fundamentally different from the thioesterase/cyclase-catalyzed polyketide chain releasing found in bacterial and other fungal polyketide biosynthesis. Genetic data suggest that the ketosynthase domain of the polyketide synthase and the chain-releasing enzyme are important for controlling the final product structure. In addition, several post-polyketide modifications have to take place before SAMT become mature toxins.

引用

页码：455 / 464

页数：10

共 89 条

[71] INVESTIGATION OF THE MECHANISM AND STERIC COURSE OF THE REACTION CATALYZED BY 6-METHYLSALICYLIC ACID SYNTHASE FROM PENICILLIUM-PATULUM USING (R)-[1-C-13 2-H-2]MALONATE AND (S)-[1-C-13 2-H-2]MALONATE [J].