High-titer heterologous production in E. coli of lyngbyatoxin, a protein kinase C activator from an uncultured marine cyanobacterium

TitleHigh-titer heterologous production in E. coli of lyngbyatoxin, a protein kinase C activator from an uncultured marine cyanobacterium
Publication TypeJournal Article
Year of Publication2013
AuthorsOngley S.E, Bian X.Y, Zhang Y.M, Chau R., Gerwick WH, Muller R, Neilan B.A
JournalAcs Chemical Biology
Volume8
Pagination1888-1893
Date Published2013/09
Type of ArticleArticle
ISBN Number1554-8929
Accession NumberWOS:000330016700006
Keywordsassembly-line; biosynthetic gene-cluster; direct cloning; escherichia-coli; expression host; natural-products; nonribosomal peptide-synthesis; polyketide; streptomyces-coelicolor; structural requirements
Abstract

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-1) and its precursor indolactam-V (150 mg L-1). 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.

DOI10.1021/cb400189j
Short TitleACS Chem. Biol.
Integrated Research Themes: 
Student Publication: 
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