A PLP-Dependent Polyketide Chain Releasing Mechanism in the Biosynthesis of Mycotoxin Fumonisins in Fusarium verticillioides

详细信息    查看全文

• 作者：Ryan Gerber ; Lili Lou ; Liangcheng Du*
• 刊名：Journal of the American Chemical Society
• 出版年：2009
• 出版时间：March 11, 2009
• 年：2009
• 卷：131
• 期：9
• 页码：3148-3149
• 全文大小：127K
• 年卷期：v.131,no.9(March 11, 2009)
• ISSN：1520-5126

文摘

Fumonisins are polyketide-derived mycotoxins produced by several plant pathogenic fungi. The toxins cause several fatal diseases in domestic animals and are associated with esophageal cancer and neural tube defects in humans. Fumonisins contain a highly reduced, acyclic 18-carbon chain, which is synthesized by an iterative polyketide synthase (PKS). This PKS does not contain a thioesterase or cyclase domain that is found in other PKSs for the release of the covalently linked polyketide chain. In this study, we expressed the acyl carrier protein (ACP) of FUM1 and in vitro loaded acyl chains to the ACP from acyl-CoA using a promiscuous 4′-phosphopantetheinyl transferase. We then expressed FUM8, which is homologous to 2-oxoamine synthase genes, in yeast and showed that the enzyme is able to offload the acyl chains from ACP. Products resulted from the decarboxylative condensation between l-alanine and acyl-S-ACP were detected by GC−MS. The enzyme activity was dependent on pyridoxal 5′-phosphate (PLP), and C18-S-ACP was the preferred substrate. The results revealed a novel polyketide chain-releasing mechanism, in which a PLP-dependent enzyme catalyzes the termination and offloading of the polyketide chain as well as the introduction of a new carbon−carbon bond and an amino group to the chain. The mechanism is fundamentally different from the thioesterase/cyclase-catalyzed polyketide chain release found in bacterial and other fungal polyketide biosyntheses.