摘要/Abstract

多重耐药菌感染是全球最严重的公共卫生危机之一.平板霉素和平板素是针对耐甲氧西林金黄色葡萄球菌和耐万古霉素肠球菌等多种革兰氏阳性菌，均有优异抗菌活性的药物先导物.由于其优异的生物活性和新奇的分子结构，多个研究小组在过去的十余年里，对平板霉素和平板素的生物合成、全合成和半合成进行了系统研究.这些研究不仅揭示了微生物药物发现的新高通量筛选策略，而且还发现负责平板霉素和平板素生物合成基因簇，并表征了多个独特的生物合成酶，例如新颖的细菌二萜合酶和硫代羧酸的生物合成酶.通过对上述研究产生的一系列平板霉素和平板素类似物及生物活性测试，揭示了这些化合物的构效关系.平板霉素和平板素的研究是结合有机合成与生物合成，加速微生物天然产物药物发现和开发的范例.综述了平板霉素和平板素的近期研究进展.
关键词: 平板霉素, 平板素, 抗生素, 生物合成, 全合成, 半合成
The emergence of multi-drug resistant bacteria is one of the major public heath crises. Platensimycin (PTM) and platencin (PTN) are potent antibacterial drug leads against many gram-postive pathogens, such as methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus. The past decade has witnessed the systematic study of biosynthesis, total synthesis and semisynthesis of these facinating molecules, due to their novel structures and excellent biological activities in vitro and in vivo. These studies have shed new lights on the disovery of microbial drug leads through novel high throughput strategies. Dedicated enzymes for the formation of PTM and PTN and other metabolites in their biosynthetic pathways, including new-characterized bacterial diterpenoid synthases and thiocarboxylate biosynthetic enzymes, have been revealed. The generation of many analogues of PTM and PTN though organic synthesis and precursor-directed biosynthesis has helped to establish the structure-activity relationships of PTM, PTN and their analgues. This review summarizes the progress in the disovery and development of these outstanding natural product drug leads, which supports the notion to integrate biosynthesis and organic synthesis for rapid microbial drug discovery and development.
Key words: platensimycin, platencin, antibiotic, biosynthesis, total synthesis, semisynthesis


PDF全文下载地址:

点我下载PDF