Sequencing and analysis of genes involved in the biosynthesis of a vancomycin group antibiotic

Sequencing and analysis of genes involved in the biosynthesis of a vancomycin group antibiotic

Background: The emergence of resistance to vancomycin, the drug of choice against methicillin-resistant Staphylococcus aureus, in enterococci has increased the need for new antibiotics. As chemical modification of the antibiotic structure is not trivial, we have initiated studies towards enzymatic m...

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Bibliographic Details
Published in:Chemistry & biology Vol. 5; no. 3; pp. 155 - 162
Main Authors: van Wageningen, AndréM.A., Kirkpatrick, Peter N., Williams, Dudley H., Harris, Barbara R., Kershaw, Jo K., Lennard, Nicola J., Jones, M., Jones, Steven J.M., Solenberg, Patricia J.
Format: Journal Article
Language:English
Published: United States Elsevier Ltd 01-03-1998
Subjects:
Actinobacteria - genetics
Anti-Bacterial Agents - biosynthesis
Anti-Bacterial Agents - chemistry
antibiotic biosynthesis
Bacteria - genetics
Chlorine - chemistry
chloroeremomycin
DNA sequence
DNA, Bacterial
Genes, Bacterial
glycopeptides
Glycosyltransferases - chemistry
Molecular Sequence Data
Open Reading Frames
Oxidation-Reduction
Protein Conformation
Vancomycin - analogs & derivatives
Vancomycin - biosynthesis
Vancomycin - chemistry
DNA sequence
chloroeremomycin
glycopeptides
antibiotic biosynthesis
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Summary:Background: The emergence of resistance to vancomycin, the drug of choice against methicillin-resistant Staphylococcus aureus, in enterococci has increased the need for new antibiotics. As chemical modification of the antibiotic structure is not trivial, we have initiated studies towards enzymatic modification by sequencing the DNA coding for the biosynthesis of chloroeremomycin (also known as A82846B and LY264826). Results: Analysis of 72 kilobases of genomic DNA from Amycolatopsis orientalis, the organism that produces chloroeremomycin, revealed the presence of 39 putative genes, including those coding for the biosynthesis of the antibiotic. Translation and subsequent comparison with known proteins in public databases identified enzymes responsible for the biosynthesis of the heptapeptide backbone and 4- epi-vancosamine, as well as those for chlorination and oxidation reactions involved in the biosynthesis of Chloroeremomycin. Conclusions: The genes responsible for the biosynthesis of chloroeremomycin have been identified, and selective expression of these genes could lead to the synthesis of new potent glycopeptide antibiotics.
Bibliography:ObjectType-Article-2
SourceType-Scholarly Journals-1
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ISSN:1074-5521
1879-1301
DOI:10.1016/S1074-5521(98)90060-6