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

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。

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

Abstract Glycopeptide antibiotics and cyclo-lipopeptide antibiotics constitute two classes of clinicallyimportant anti-infective drugs, and some of them have been approved for clinic therapy for severe infection caused bymultidrug resistant organisms, such as vancomycin, teicoplanin, dalbavancin, telavancin, polymyxin, daptomycin, andcaspofungin. The chemical structure of most of the two classes of antibiotics contain sundry branched chain fatty acidside-chains (BCFAs). The differences in BCFAs is the main reason of structural diversity of glycopeptide antibioticsand cyclo-lipopeptide antibiotics. The biosynthsis of BCFAs usually starts from the catabolism of branched-chainamino acid (BCAAs), leucine, isoleucine, and valine. Regulating metabolic pathways of BCAAs has an importantsignificance for directional biosynthesis of glycopeptide antibiotics and cyclo-lipopeptide antibiotics. In thisreview, the biosynthetic origin of BCFAs of glycopeptide antibiotics and cyclo-lipopeptide antibiotics, exogenouslyadding specific BCAAs to regulate the yield and component during glycopeptide and gyclo-lipopeptide antibioticsfermentation, and the endogenously knockout of key gene clusters encoding branched-chain α-ketoacid dehydrogenasecomplex (BCKD) for BCAAs catabolism in order to regulate the yield and component during glycopeptide and gyclolipopeptideantibiotics fermentation were