噻唑肽类抗生素研究进展

Recent developments in thiazole-peptides

多数噻唑肽类抗生素能与细菌的50s核糖体亚基相结合抑制其蛋白质的合成,有些还能抑制肾素-血管紧张素系统。产生抗性的链霉菌可以合成一种甲基转移酶,将自身的23SrRNA1067位点上的腺苷2’-OH转化成2’-CH3,阻碍噻唑肽类抗生素与50s核糖体亚基结合。通过研究噻唑肽类化合物生物合成基因发现,产生该类抗生素的劳伦链霉菌和活力链霉菌中均含有编码非核糖体合成酶的基因。因此噻唑肽类化合物极可能是由非核糖体肽合成酶(NRPS)根据巯基模板机制装配而成。本文重点就噻唑肽类化合物的作用机制、抗性机制以及合成途径的研究进展进行综述。

Most thiazole-petide antibiotics inhibit protein synthesis in bacteria by binding to the 50S ribosomal subunit ; Some are discovered as renin inhibitors. In the resistant strains of streptomycetes, there are some enzymes that methylate the 2＇-OH of adenosine 1067 in the 23S rRNA. This methylation confers resis- tance to thiazole-petides by preventing antibiotics binding. Progress toward cloning the biosynthetic machinery suggests that thiazole-peptide-producing microorganism. Streptomyces laurentii and Streptomyces actuosus contain genes that encode the NRPS. Therefore, thiazole-ptides are most probably formed by nonribosomal peptide synthetases （NRPS） through the thiotemplate pathway. The mechanisms of action, resistance and the mode for thiazole-pide biosynthesis are reviewed.