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Enzymatic generation of the antimetabolite gamma,gamma-dichloroaminobutyrate by NRPS and mononuclear iron halogenase action in a streptomycete CHEMISTRY & BIOLOGY Ueki, M., Galonic, D. P., Vaillancourt, F. H., Garneau-Tsodikova, S., Yeh, E., Vosburg, D. A., Schroeder, F. C., Osada, H., Walsh, C. T. 2006; 13 (11): 1183-1191

Abstract

Four adjacent open reading frames, cytC1-C4, were cloned from a cytotrienin-producing strain of a Streptomyces sp. by using primers derived from the conserved region of a gene encoding a nonheme iron halogenase, CmaB, in coronamic acid biosynthesis. CytC1-3 were active after expression in Escherichia coli, and CytC4 was active after expression in Pseudomonas putida. CytC1, a relatively promiscuous adenylation enzyme, installs the aminoacyl moieties on the phosphopantetheinyl arm of the holo carrier protein CytC2. CytC3 is a nonheme iron halogenase that will generate both gamma-chloro- and gamma,gamma-dichloroaminobutyryl-S-CytC2 from aminobutyryl-S-CytC2. CytC4, a thioesterase, hydrolytically releases the dichloroaminobutyrate, a known streptomycete antibiotic. Thus, this short four-protein pathway is likely the biosynthetic source of this amino acid antimetabolite. This four-enzyme system analogously converts the proS-methyl group of valine to the dichloromethyl product regio- and stereospecifically.

View details for DOI 10.1016/j.chembiol.2006.09.012

View details for Web of Science ID 000242418400010

View details for PubMedID 17114000