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 γ-chloro- and γ,γ-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.
Original language | English |
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Pages (from-to) | 1183-1191 |
Number of pages | 9 |
Journal | Chemistry and Biology |
Volume | 13 |
Issue number | 11 |
DOIs | |
State | Published - Nov 2006 |
Bibliographical note
Funding Information:This work was supported in part by National Institutes of Health (NIH) grants GM 20011 and GM 49338 (C.T.W.), a Damon Runyon Cancer Research Foundation Postdoctoral Fellowship (DRG-1893-05 to D.P.G.), a Merck-sponsored Fellowship of the Helen Hay Whitney Foundation (F.H.V.), a Natural Sciences and Engineering Research Council Postdoctoral Fellowship (F.H.V.), an NIH Medical Scientist Training Program Fellowship (E.Y.), and a Jane Coffin Childs Memorial Fund for Medical Research Fellowship (D.A.V.).
Keywords
- CHEMBIO
- MICROBES
ASJC Scopus subject areas
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Pharmacology
- Drug Discovery
- Clinical Biochemistry