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
程坤 1卫禾耕 2杨伟强 3盛清 4杨仲毅5
作者信息
- 1. 浙江理工大学生命科学与医药学院,浙江 杭州 310018;台州学院药学院,浙江台州 318000
- 2. 浙江永太科技股份有限公司,浙江台州 317016
- 3. 浙江海洲制药股份有限公司,浙江台州 317016
- 4. 浙江理工大学生命科学与医药学院,浙江 杭州 310018
- 5. 台州学院药学院,浙江台州 318000
- 折叠
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-Gin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-Gin工业化生产的首选工艺技术.
Abstract
L-alanyl-L-glutamine(Ala-Gln)is an important dipeptide in modern medical and health care.After en-tering 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 and a-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.a-amino acid ester ac-yltransferase synthesizes Ala-Gin from L-alanine methyl ester and L-glutamine,and the related research mainly focuses on the enzyme expression system,directional evolution,and immobilisation.a-amino acid ester acyltransferase can con-vert and produce 106.61 g/L of Ala-Gln in 25 min.Compared with microbial fermentation,this method has a shorter re-action 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Key words
L-alanyl-L-glutamine(Ala-Gln)/microbial fermentation/biocatalysis/L-amino acid ligase/a-amino acid ester acyltransferase/biosynthesis引用本文复制引用
出版年
2024
国家科技期刊平台
NSTL
万方数据