生物法生产3-羟基丙酸研究进展  

Recent progress in microbial production of 3-hydroxypropionic acid

作　　者：于新磊 毛雨丰 张晓霞 陆凌雪[1,2,3] 王智文 陈涛[1,2,3] YU Xinlei;MAO Yufeng;ZHANG Xiaoxia;LU Lingxue;WANG Zhiwen;CHEN Tao(School of Chemical Engineering and Technology,Tianjin University,Tianjin 300345,China;Key Laboratory of Systems Bioengineering(Ministry of Education),Tianjin University,Tianjin 300345,China;Collaborative Innovation Center of Chemical Science and Engineering(Tianjin),Tianjin 300350,China)

机构地区：[1]天津大学化工学院,天津300345 [2]天津大学系统生物工程教育部重点实验室,天津300345 [3]天津化学化工协同创新中心,天津300350

出　　处：《化工进展》2018年第11期4427-4436,共10页Chemical Industry and Engineering Progress

基　　金：国家自然科学基金项目(21776208;21390201;21621004)

摘　　要：3-羟基丙酸(3-hydroxypropionic acid,3-HP)是一种具有末端羟基与羧基双活性基团、应用广泛的有机酸,生物法合成3-HP具有高效、绿色、可持续发展等优势。本文分析了生物法生产3-HP的主要合成途径、主要生产菌种及菌株改造、发酵工艺优化3个方面的研究进展。重点介绍了以甘油合成途径、丙二酰辅酶A合成途径、β-丙氨酸合成途径为代表的主要合成途径及相应途径的关键酶;以克雷伯氏肺炎球菌、酵母菌及大肠杆菌为代表的主要生产菌株及其改造策略;包括分批发酵、两阶段发酵及固定化细胞催化等在内的发酵工艺优化策略3个方面的研究内容。最后指出了进一步筛选改造甘油脱水酶等途径的关键酶;基于先进基因组编辑技术开发的非致病性、3-HP高耐受型菌株,挖掘新的3-HP合成途径;开发更加经济、高效、环保的发酵工艺路线,将是今后生物法生产3-HP的研究重点。3-Hydroxypropionic acid(3-HP)is an organic acid with terminal hydroxy and carboxyl reactive groups and has wide applications in many industrial sectors.Biosynthesis of 3-HP is highly efficient,green and sustainable.In this review,the authors analyzed the major synthetic pathways of 3-HP bio-production,representative production hosts,strategies of strain development,and optimization of fermentation parameters.The review focused on the recent research progresses on the following aspects,including major 3-HP pathways such as glycerol pathway;malonyl-CoA pathway;β-alanine pathway and key enzymes of each pathway,representative 3-HP production hosts such as Klebsiella pneumoniae;Saccharomyces and Escherichia coli and strategies of strain development,optimization of 3-HP bio-production processes such as batch operation;two-stage fermentation and immobilized cell fermentation.In the end,the authors pointed out that screening of key enzymes like glycerol dehydratase,development of novo 3-HP synthetic pathways and non-pathogenic production host with high 3-HP tolerance via advanced genomic editing technique and development of more economic;highly efficient and environmental friendly bio-production process are vital research topics in the future.

关 键 词：3-羟基丙酸 微生物发酵 代谢工程 工程菌株 生物合成途径 甘油脱水酶 

分 类 号：Q756[生物学—分子生物学] Q815