丙谷二肽的生物合成及关键酶研究进展  

Progress in biosynthesis and key enzymes of Ala-Gln

作　　者：程坤 卫禾耕 杨伟强 盛清[1] 杨仲毅[2] CHENG Kun;WEI Hegeng;YANG Weiqiang;SHENG Qing;YANG Zhongyi(College of Life Sciences and Medicine,Zhejiang Sci-Tech University,Hangzhou 310018,Zhejiang,China;School of Pharmaceutical Science,Taizhou University,Taizhou 318000,Zhejiang,China;Zhejiang Yongtai Technology Co.,Ltd.,Taizhou 317016,Zhejiang,China;Zhejiang Haizhou Pharmaceutical Co.,Ltd.,Taizhou 317016,Zhejiang,China)

机构地区：[1]浙江理工大学生命科学与医药学院,浙江杭州310018 [2]台州学院药学院,浙江台州318000 [3]浙江永太科技股份有限公司,浙江台州317016 [4]浙江海洲制药股份有限公司,浙江台州317016

出　　处：《生物资源》2024年第6期538-550,共13页Biotic Resources

基　　金：浙江理工大学绍兴生物医药研究院开放基金(SXAB202007)。

摘　　要：丙谷二肽(L-alanyl-L-glutamine,Ala-Gln)是目前发现的一种在现代医疗健康领域极其重要的二肽,其进入人体后能够迅速水解成L-谷氨酰胺,促进蛋白质合成。生物合成丙谷二肽具有绿色、高效、安全的优点,主要的生物合成途径有微生物发酵法和生物催化法,其关键酶分别是L-氨基酸连接酶和α-氨基酸酯酰基转移酶。通过敲除dpp、pep等基因来抑制二肽的降解,发酵法中Ala-Gln的最高水平为24.70 g/L,发酵时间为47 h。α-氨基酸酯酰基转移酶以L-丙氨酸甲酯和L-谷氨酰胺为原料合成Ala-Gln,相关研究主要集中在酶的表达体系、定向进化、固定化等领域。α-氨基酸酯酰基转移酶可以在25 min转化生成106.61 g/L的Ala-Gln,相较于微生物发酵法,该方法的反应时间更短,产物浓度更高,且无须ATP供能,是Ala-Gln工业化生产的首选工艺技术。L-alanyl-L-glutamine(Ala-Gln)is an important dipeptide in modern medical and health care.After entering the human body,it can be rapidly hydrolyzed into L-glutamine,which promotes protein synthesis.The synthesis of Ala-Gln dipeptide by biological method has the advantages of green,high efficiency and safety.The main biosynthetic pathways are microbial fermentation and biocatalysis,whose key enzymes are L-amino acid ligase andα-amino acid ester acyltransferase.The degradation of dipeptide can be inhibited by knocking out genes such as dpp and pep,and the highest level of Ala-Gln in the fermentation method can reach 24.70 g/L after a fermentation time of 47 h.α-amino acid ester acyltransferase synthesizes Ala-Gln from L-alanine methyl ester and L-glutamine,and the related research mainly focuses on the enzyme expression system,directional evolution,and immobilisation.α-amino acid ester acyltransferase can convert and produce 106.61 g/L of Ala-Gln in 25 min.Compared with microbial fermentation,this method has a shorter reaction time,higher product concentration,and does not need ATP for energy supply,making it the preferred process technology for industrial production of Ala-Gln.

关 键 词：丙谷二肽 微生物发酵 生物催化 L-氨基酸连接酶 α-氨基酸酯酰基转移酶 生物合成 

分 类 号：TQ464[化学工程—制药化工]