Institute of Gene Biology, Russian Academy of Sciences, Moscow 119334, Russia.
J Biol Chem. 2010 Apr 23;285(17):12662-9. doi: 10.1074/jbc.M109.080192. Epub 2010 Feb 16.
The heptapeptide-nucleotide microcin C (McC) is a potent inhibitor of enteric bacteria growth. McC is excreted from producing cells by the MccC transporter. The residual McC that remains in the producing cell can be processed by cellular aminopeptidases with the release of a non-hydrolyzable aspartyl-adenylate, a strong inhibitor of aspartyl-tRNA synthetase. Accumulation of processed McC inside producing cells should therefore lead to translation inhibition and cessation of growth. Here, we show that a product of another gene of the McC biosynthetic cluster, mccE, acetylates processed McC and converts it into a non-toxic compound. MccE also makes Escherichia coli resistant to albomycin, a Trojan horse inhibitor unrelated to McC that, upon processing, gives rise to a serine coupled to a thioxylofuranosyl pyrimidine, an inhibitor of seryl-tRNA synthetase. We speculate that MccE and related cellular acetyltransferases of the Rim family may detoxify various aminoacyl-nucleotides, either exogenous or those generated inside the cell.
七肽核苷酸类微菌素 C(McC)是一种强效的肠道细菌生长抑制剂。McC 通过 MccC 转运蛋白从产生细胞中分泌出来。残留在产生细胞中的残留 McC 可以被细胞氨肽酶处理,释放出不可水解的天冬氨酰-腺苷酸,这是天冬氨酰-tRNA 合成酶的强抑制剂。因此,产生细胞内积累的加工 McC 应该会导致翻译抑制和生长停止。在这里,我们表明 McC 生物合成簇的另一个基因 mccE 的产物乙酰化加工后的 McC,并将其转化为无毒化合物。MccE 还使大肠杆菌对 albomycin 产生抗性,albomycin 是一种与 McC 无关的特洛伊木马抑制剂,在加工后会产生与硫氧呋喃嘧啶连接的丝氨酸,这是丝氨酰-tRNA 合成酶的抑制剂。我们推测 MccE 和 Rim 家族的相关细胞乙酰转移酶可能会解毒各种氨酰核苷酸,无论是外源性的还是细胞内产生的。