title: Sequencing and analysis of genes involved in the biosynthesis of a vancomycin group antibiotic.
abstract: 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.
authors.affiliation: Cambridge Centre for Molecular Recognition, Department of Chemistry, Cambridge, UK.
authors.forename: A M
authors.initials: AM
authors.lastname: van Wageningen
authors.forename: P N
authors.initials: PN
authors.lastname: Kirkpatrick
authors.forename: D H
authors.initials: DH
authors.lastname: Williams
authors.forename: B R
authors.initials: BR
authors.lastname: Harris
authors.forename: J K
authors.initials: JK
authors.lastname: Kershaw
authors.forename: N J
authors.initials: NJ
authors.lastname: Lennard
authors.forename: M
authors.initials: M
authors.lastname: Jones
authors.forename: S J
authors.initials: SJ
authors.lastname: Jones
authors.forename: P J
authors.initials: PJ
authors.lastname: Solenberg
mesh_terms: D039903:Actinobacteria / Q000235:genetics; D000900:Anti-Bacterial Agents / Q000096:biosynthesis* / Q000737:chemistry; D001419:Bacteria / Q000235:genetics; D002713:Chlorine / Q000737:chemistry; D004269:DNA, Bacterial; D005798:Genes, Bacterial; D016695:Glycosyltransferases / Q000737:chemistry; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D010084:Oxidation-Reduction; D011487:Protein Conformation; D014640:Vancomycin / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000737:chemistry
chemical_list: D000900:Anti-Bacterial Agents; D004269:DNA, Bacterial; C112142:chloroeremomycin; D002713:Chlorine; D014640:Vancomycin; D016695:Glycosyltransferases