Tahlan Kapil, Anders Cecilia, Wong Annie, Mosher Roy H, Beatty Perrin H, Brumlik Michael J, Griffin Allison, Hughes Claire, Griffin John, Barton Barry, Jensen Susan E
Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada.
Chem Biol. 2007 Feb;14(2):131-42. doi: 10.1016/j.chembiol.2006.11.012.
The Streptomyces clavuligerus clavam gene cluster was examined to identify genes specifically involved in 5S clavam biosynthesis. A reduction/loss of 5S clavam production was seen in cvm2 and cvm5 gene mutants, and a clavam metabolite not previously observed, 2-carboxymethylideneclavam, accumulated in the cvm5 mutant. Disruption of additional genes from the region of the clavam cluster did not have any effect on 5S clavam production. Examination of the paralog gene cluster region for 5S clavam biosynthetic genes led to the identification of cvm6P and cvm7P, which encode a putative aminotransferase and a transcriptional regulator, respectively. Mutants defective in cvm6P and cvm7P were completely blocked in 5S clavam but not clavulanic acid production. The loss of 5S clavam production in cvm7P mutants suggests that this gene encodes a transcriptional regulator specific for 5S clavam metabolite biosynthesis.
对产黄青霉棒酸基因簇进行了研究,以鉴定专门参与5S棒酸生物合成的基因。在cvm2和cvm5基因突变体中观察到5S棒酸产量降低/丧失,并且在cvm5突变体中积累了一种以前未观察到的棒酸代谢物2-羧基亚甲基棒酸。破坏棒酸簇区域中的其他基因对5S棒酸产量没有任何影响。对5S棒酸生物合成基因的旁系同源基因簇区域进行研究,鉴定出了cvm6P和cvm7P,它们分别编码一种假定的转氨酶和一种转录调节因子。cvm6P和cvm7P有缺陷的突变体在5S棒酸而非克拉维酸的生产中完全受阻。cvm7P突变体中5S棒酸产量的丧失表明该基因编码一种对5S棒酸代谢物生物合成具有特异性的转录调节因子。