High-Titer Heterologous Production in E. coli of Lyngbyatoxin, a Protein Kinase C Activator from an Uncultured Marine Cyanobacterium

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• 作者：Sarah E. Ongley ; Xiaoying Bian ; Youming Zhang ; Rocky Chau ; William H. Gerwick ; Rolf M眉ller ; Brett A. Neilan
• 刊名：ACS Chemical Biology
• 出版年：2013
• 出版时间：September 20, 2013
• 年：2013
• 卷：8
• 期：9
• 页码：1888-1893
• 全文大小：292K
• 年卷期：v.8,no.9(September 20, 2013)
• ISSN：1554-8937

文摘

Many chemically complex cyanobacterial polyketides and nonribosomal peptides are of great pharmaceutical interest, but the levels required for exploitation are difficult to achieve from native sources. Here we develop a framework for the expression of these multifunctional cyanobacterial assembly lines in Escherichia coli using the lyngbyatoxin biosynthetic pathway, derived from a marine microbial assemblage dominated by the cyanobacterium Moorea producens. Heterologous expression of this pathway afforded high titers of both lyngbyatoxin A (25.6 mg L^鈥?) and its precursor indolactam-V (150 mg L^鈥?). Production, isolation, and identification of all expected chemical intermediates of lyngbyatoxin biosynthesis in E. coli also confirmed the previously proposed biosynthetic route, setting a solid chemical foundation for future pathway engineering. The successful production of the nonribosomal peptide lyngbyatoxin A in E. coli also opens the possibility for future heterologous expression, characterization, and exploitation of other cyanobacterial natural product pathways.