School of Biological Sciences, Seoul National University, Seoul 151-747, South Korea.
Appl Microbiol Biotechnol. 2010 Oct;88(3):659-69. doi: 10.1007/s00253-010-2801-2. Epub 2010 Aug 14.
Clavulanic acid, a β-lactamase inhibitor, is used together with β-lactam antibiotics to create drug mixtures possessing potent antimicrobial activity. In view of the clinical and industrial importance of clavulanic acid, identification of the clavulanic acid biosynthetic pathway and the associated gene cluster(s) in the main producer species, Streptomyces clavuligerus, has been an intriguing research question. Clavulanic acid biosynthesis was revealed to involve an interesting mechanism common to all of the clavam metabolites produced by the organism, but different from that of other β-lactam compounds. Gene clusters involved in clavulanic acid biosynthesis in S. clavuligerus occupy large regions of nucleotide sequence in three loci of its genome. In this review, clavulanic acid biosynthesis and the associated gene clusters are discussed, and clavulanic acid improvement through genetic manipulation is explained.
克拉维酸是一种β-内酰胺酶抑制剂，与β-内酰胺抗生素联合使用，可以制成具有强大抗菌活性的药物混合物。鉴于克拉维酸的临床和工业重要性，确定主要生产菌——棒状链霉菌中的克拉维酸生物合成途径和相关基因簇一直是一个有趣的研究问题。克拉维酸的生物合成涉及到一种有趣的机制，这种机制与该生物产生的所有克拉维烷类代谢物都相同，但与其他β-内酰胺化合物的机制不同。棒状链霉菌中参与克拉维酸生物合成的基因簇占据了其基因组三个基因座中大片段的核苷酸序列。本文讨论了克拉维酸的生物合成及其相关基因簇，并解释了通过遗传操作来提高克拉维酸的产量。
