Investigating the clavam gene cluster in Streptomyces antibioticus Tü1718

Sarah Goomeshi Nobary
2011
Production of clavams (including clavulanic acid, a potent β-lactamase inhibitor) has been studied in Streptomyces clavuligerus. All clavams share the early biosynthetic steps. However, many of the late steps of the pathway remain unclear. Streptomyces antibioticus Tü1718 was chosen for this study because it produces two 5S clavams (different from clavulanic acid in their stereochemistry) and no clavulanic acid. After screening a cosmid library of the gDNA of this bacterium for a cas gene
more » ... ing an early biosynthetic enzymes), a cosmid was selected. After finding additional early genes (bls, pah, ceaS, oat) and some putative late pathway genes (an aminotransferase and ORFs similar to c7p, cvm1 and orfA of S. clavuligerus) in the regions flanking cas, the whole cosmid was sequenced. Several novel genes were encountered including ntr that showed similarity to a nitroreductase. Knock out mutation of the cas and ntr gene abolished clavam production in S. antibioticus Tü1718.
doi:10.7939/r3d93t fatcat:yl2kxegstzbnvolsteyc4xlzoe