Document Detail


Thiostrepton biosynthesis: prototype for a new family of bacteriocins.
MedLine Citation:
PMID:  19265401     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Thiopeptide antibiotics are a group of highly modified peptide metabolites. The defining scaffold for the thiopeptides is a macrocycle containing a dehydropiperidine or pyridine ring, dehydrated amino acids, and multiple thiazole or oxazole rings. Some members of the thiopeptides, such as thiostrepton, also contain either a quinaldic acid or indolic acid substituent derived from tryptophan. Although the amino acid precursors of these metabolites are well-established, the biogenesis of these complex peptides has remained elusive. Whole-genome scanning of Streptomyces laurentii permitted identification of a thiostrepton prepeptide, TsrA, and involvement of TsrA in thiostrepton biosynthesis was confirmed by mutagenesis. A gene cluster responsible for thiostrepton biosynthesis is reported, and the encoded gene products are discussed. The disruption of a gene encoding an amidotransferase, tsrT, led to the loss of thiostrepton production and the detection of a new metabolite, contributing further support to the identification of the tsr cluster. The tsr locus also appears to possess the gene products needed to convert tryptophan to the quinaldic acid moiety, and an aminotransferase was found to catalyze an early step in this pathway. This work establishes that the thiopeptides are a type of bacteriocin, a family of genetically encoded antimicrobial peptides, and are subjected to extensive posttranslational modification during maturation of the prepeptide.
Authors:
Wendy L Kelly; Lisa Pan; Chaoxuan Li
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of the American Chemical Society     Volume:  131     ISSN:  1520-5126     ISO Abbreviation:  J. Am. Chem. Soc.     Publication Date:  2009 Apr 
Date Detail:
Created Date:  2009-03-25     Completed Date:  2009-07-28     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7503056     Medline TA:  J Am Chem Soc     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4327-34     Citation Subset:  IM    
Affiliation:
School of Chemistry and Biochemistry and the Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia 30332, USA. wendy.kelly@chemistry.gatech.edu
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MeSH Terms
Descriptor/Qualifier:
Anti-Bacterial Agents / chemistry,  pharmacology
Bacteriocins / chemistry*,  genetics*
Chromatography, High Pressure Liquid
Cloning, Molecular
Escherichia coli / genetics
Genetic Techniques
Models, Chemical
Models, Genetic
Multigene Family
Open Reading Frames
Peptides / chemistry
Polymerase Chain Reaction
Streptomyces / metabolism
Thiazoles / chemistry
Thiostrepton / biosynthesis*,  chemistry*
Chemical
Reg. No./Substance:
0/Anti-Bacterial Agents; 0/Bacteriocins; 0/Peptides; 0/Thiazoles; 1393-48-2/Thiostrepton

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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