糖肽抗生素天然产物研究进展  

Research progress of glycopeptide antibiotics

作　　者：郭蔚[1] 李星坤 邓子新 侯安伟 徐敏 GUO Wei;LI XingKun;DENG ZiXin;HOU AnWei;XU Min(Tianjin Institute of Industrial Biotechnology,Chinese Academy of Sciences,Tianjin 300308,China;Haihe Laboratory of Synthetic Biology,Tianjin 300308,China)

机构地区：[1]中国科学院天津工业生物技术研究所,天津300308 [2]合成生物学海河实验室,天津300308

出　　处：《中国科学:生命科学》2025年第4期661-680,共20页Scientia Sinica(Vitae)

基　　金：国家重点研发计划(2023YFA0916200);天津市合成生物技术创新能力提升行动项目(TSBICIP-CXRC-065,TSBICIP-CXRC-076);合成生物学海河实验室重大攻关类和颠覆性创新项目(22HHSWSS00001,22HHSWSS00007);国家自然科学基金(22107038)资助。

摘　　要：糖肽抗生素(Glycopeptide antibiotics,GPA)是临床上用于治疗耐药革兰氏阳性病原菌感染的重要药物.不幸的是,随着GPA的应用,临床上也陆续发现了万古霉素耐药肠球菌与金黄色葡萄球菌感染的病例,使得相关病原菌感染的医治愈发困难.为了应对糖肽抗生素耐药的临床威胁,我们需要持续不断地去开发新一代高效GPA.微生物天然产物是临床药物的主要来源,其中GPA均来自放线菌天然产物.(宏)基因组测序显示,放线菌基因组中携带大量编码GPA生物合成的基因簇,是新一代GPA的资源宝库.本文系统性地回顾了GPA的发现史,总结了GPA的生物合成机制、作用机制、耐药机制以及最新的发掘方法与策略,以期为GPA的开发提供参考.Glycopeptide antibiotics(GPA)are critical medicines for the clinical treatment of multiple drug resistant Gram-positive pathogens.Unfortunately,the emergence of infections caused by vancomycin resistant Enterococcus and Staphylococcus aureus because of the clinical application of GPA has making the treatment increasingly difficult.In order to tackle the growing GPA resistant threat,continuous efforts need to be implemented for searching GPAs with higher potency.Microbial natural products is the main source of clinically important drugs,in particular,GPAs are all produced by bacteria from the phylum of Actinobacteria.(Meta)Genome sequencing has revealed dozens of GPA biosynthetic gene clusters in the genome of actinobacteria,representing an untapped treasure trove for next-generation GPA.This review describes the discovery of GPA and summarizes the biosynthesis,mode of action,mechanism of resistance,and innovative mining strategies for GPA to provide clues for the development of new GPAs.

关 键 词：天然产物 糖肽抗生素 抗生素耐药 生物合成 基因组挖掘 

分 类 号：R978.1[医药卫生—药品]