title: A comparison of the clavam biosynthetic gene clusters in  Streptomyces antibioticus  Tü1718 and  Streptomyces clavuligerus.
abstract: The production of clavam metabolites has been studied previously in  Streptomyces clavuligerus , a species that produces clavulanic acid as well as 4 other clavam compounds, but the late steps of the pathway leading to the specific end products are unclear. The present study compared the clavam biosynthetic gene cluster in  Streptomyces antibioticus , chosen because it produces only 2 clavam metabolites and no clavulanic acid, with that of S. clavuligerus. A cosmid library of S. antibioticus genomic DNA was screened with a clavaminate synthase-specific probe based on the corresponding genes from S. clavuligerus, and 1 of the hybridizing cosmids was sequenced in full. A clavam gene cluster was identified that shows similarities to that of S. clavuligerus but also contains a number of novel genes. Knock-out mutation of the clavaminate synthase gene abolished clavam production in S. antibioticus, confirming the identity of the gene cluster. Knock-out mutation of a novel gene encoding an apparent oxidoreductase also abolished clavam production. A potential clavam biosynthetic pathway consistent with the genes in the cluster and the metabolites produced by S. antibioticus, and correspondingly different from that of S. clavuligerus, is proposed.
authors.affiliation: Department of Biological Sciences, University of Alberta, Edmonton, AB T6G 2E9, Canada.
authors.forename: Sarah
authors.initials: S
authors.lastname: Goomeshi Nobary
authors.forename: Susan E
authors.initials: SE
authors.lastname: Jensen
mesh_terms: D001483:Base Sequence; D002969:Clavulanic Acids / Q000096:biosynthesis*; D005798:Genes, Bacterial; D006899:Mixed Function Oxygenases / Q000378:metabolism; D008969:Molecular Sequence Data; D005810:Multigene Family; D009154:Mutation; D013302:Streptomyces / Q000235:genetics* / Q000378:metabolism; D013303:Streptomyces antibioticus / Q000235:genetics / Q000378:metabolism
chemical_list: D002969:Clavulanic Acids; C483963:clavam; D006899:Mixed Function Oxygenases; C066046:clavaminate synthase