A comparison of the clavam biosynthetic gene clusters in Streptomyces antibioticus Tu1718 and Streptomyces clavuligerus

作者：Nobary Sarah Goomeshi; Jensen Susan E^*

来源：Canadian Journal of Microbiology, 2012, 58(4): 413-425.

DOI：10.1139/W2012-012

• beta-lactam
• clavulanic acid
• valclavam
• alanylclavam
• clavamycin

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.

• 出版日期2012-4