支链氨基酸代谢在糖肽类和环脂肽类抗生素产量提高与组分优化中的应用  

The application of branched-chain amino acids metabolism regulation to increase the yields and optimizing components of glycopeptides and cyclopeptide fermentation

作　　者：李辉 方志锴[2] 郭霞凌 江红[2] Li Hui;Fang Zhi-kai;Guo Xia-ling;Jiang Hong(Argus Pharmaceticals,Ltd.,Changsha 410221;Fujian Institute of Microbiology,Fuzhou 350007)

机构地区：[1]大邦(湖南)生物制药有限公司,长沙410221 [2]福建省微生物研究所,福州350007

出　　处：《中国抗生素杂志》2022年第3期263-269,共7页Chinese Journal of Antibiotics

基　　金：湖南省制造强省专项(No.湘财企指[2018]64);福建省公益类科研院所专项(No.2020R10050011)。

摘　　要：糖肽类和环脂肽类抗生素具有很好的抗菌活性,临床上广泛用于治疗多重耐药菌导致的严重感染。大部分糖肽类和环脂肽类抗生素均含有带支链结构的脂肪酸侧链,侧链结构差异是导致这两类抗生素发酵组分多样性的主要原因。支链脂肪酸侧链的合成起始于支链氨基酸分解代谢,调控支链氨基酸代谢对于定向合成含有特定脂肪酸侧链的糖肽类和环脂肽类抗生素具有重要作用。本文从糖肽类和环脂肽类抗生素中脂肪酸侧链的生源途径、外源添加支链氨基酸对糖肽类和环脂肽类抗生素产量和组分的影响,内部改造支链氨基酸代谢途径对糖肽类和环脂肪肽类抗生素产量和组分的影响3方面进行了综述。Glycopeptide antibiotics and cyclo-lipopeptide antibiotics constitute two classes of clinically important anti-infective drugs,and some of them have been approved for clinic therapy for severe infection caused by multidrug resistant organisms,such as vancomycin,teicoplanin,dalbavancin,telavancin,polymyxin,daptomycin,and caspofungin.The chemical structure of most of the two classes of antibiotics contain sundry branched chain fatty acid side-chains(BCFAs).The differences in BCFAs is the main reason of structural diversity of glycopeptide antibiotics and cyclo-lipopeptide antibiotics.The biosynthsis of BCFAs usually starts from the catabolism of branched-chain amino acid(BCAAs),leucine,isoleucine,and valine.Regulating metabolic pathways of BCAAs has an important significance for directional biosynthesis of glycopeptide antibiotics and cyclo-lipopeptide antibiotics.In this review,the biosynthetic origin of BCFAs of glycopeptide antibiotics and cyclo-lipopeptide antibiotics,exogenously adding specific BCAAs to regulate the yield and component during glycopeptide and gyclo-lipopeptide antibiotics fermentation,and the endogenously knockout of key gene clusters encoding branched-chainα-ketoacid dehydrogenase complex(BCKD)for BCAAs catabolism in order to regulate the yield and component during glycopeptide and gyclolipopeptide antibiotics fermentation were summarized.

关 键 词：糖肽类抗生素 环脂肽类抗生素 支链脂肪酸 支链氨基酸 发酵 组分 产量 

分 类 号：R978.1[医药卫生—药品]