一碳生物转化合成有机酸的研究进展

Bioconversion of one carbon feedstocks for producing organic acids

有机酸在食品、医药、化工、农业等领域有着广泛的应用。目前有机酸的生产主要以微生物发酵法为主,采用糖类为原料,然而长此以往可能面临“与人争粮”的困境。CO、CO_(2)、甲烷、甲醇和甲酸等含有一个碳原子的物质被称为一碳(one carbon,C_(1))资源,其来源广泛且价格低廉,有望成为生物制造的替代原料,且C_(1)原料生物转化有助于缓解温室效应、助力“碳中和”目标。本文总结了近年来CO_(2)、甲烷和甲醇生物合成3种重要有机酸(3-羟基丙酸、乳酸、琥珀酸)的研究进展,主要论述了C_(1)生物利用途径、有机酸的生物合成途径以及代谢工程策略,也讨论了C_(1)合成有机酸的挑战及应对措施,并展望了有机酸产业化新路线,尤其是化学催化与生物转化耦合以CO_(2)为原料合成有机酸。本综述对于C_(1)生物炼制以及有机酸产业升级具有一定的参考意义。

Organic acids,as important platform chemicals,have been widely used in food,pharmaceutical,chemical industries and agriculture.Currently,microbial production of organic acids relies primarily on sugars as feedstocks,which may suffer from the competition with food and arable lands.One carbon(C_(1))molecules such as CO,CO_(2),methane,methanol and formic acid are widespread and inexpensive,which are considered as ideal feedstocks for future bio-manufacturing.Bioconversion of C_(1) feedstocks toward the production of organic acids helps mitigate greenhouse effect and realize carbon neutrality.Therefore C_(1) sources have been regarded as raw materials of third generation biorefinery,and natural C_(1) utilizing microbes attracted increasing attention.Although some microorganisms have native biosynthetic pathway of organic acids,the production efficiency is usually lower than expected.This review summarizes the recent progress on the biosynthesis of organic acids(3-hydroxypropionic acid,lactic acid and succinic acid)from C_(1) feedstocks using synthetic biology methods.First,the native C_(1) utilizing pathways are summarized,including CO_(2),CO,methane,methanol and formic acid.Then the metabolic engineering strategies to improve organic acids production were systematically reviewed,including the optimization of rate-limiting enzymes expression,enhancement of the supply of precursor and cofactor,cofactor engineering,and inhibition of the product degradation.In addition,the challenges,solutions,and prospects of C_(1) bioconversion to organic acids are also discussed,and coupling chemical catalysis and biological transformation may provide a promising industrial route for organic acids production.In particular,methanol is an ideal C_(1) feedstock with many advantages like convenient storage and transportation,high liquid-to-liquid mass transfer efficiency,and it can also be massively produced from CO_(2) by“liquid sunshine”technology.Therefore constructing high efficient methanol cell factory may enable organic acids production from CO_(2),a carbon neutral production manner.This review may provide a guidance for C_(1) biorefinery and industrial bioproduction of organic acids.