生物法生产3-羟基丙酸研究进展

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。

Recent progress in microbial production of 3-hydroxypropionic acid

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.