甲酸微生物转化研究进展

doi:10.16085/j.issn.1000-6613.2022-1546

化工进展 ›› 2023, Vol. 42 ›› Issue (1): 67-72.DOI: 10.16085/j.issn.1000-6613.2022-1546

• —碳化合物生物利用与转化 • 上一篇下一篇

甲酸微生物转化研究进展

赵同心¹(), 赵磊¹^,²(), 张延平¹(), 李寅¹

^1.中国科学院微生物生理与代谢工程重点实验室，微生物资源前期开发国家重点实验室，中国科学院微生物研究所，北京 100101
^2.中国科学院大学，北京 100049

收稿日期:2022-08-22 修回日期:2022-09-24 出版日期:2023-01-25 发布日期:2023-02-20
通讯作者: 张延平
作者简介:赵同心（1990—），女，博士，助理研究员，研究方向生物固碳及疫苗。E-mail：txzhao2014@sina.com。
赵磊（1997—），男，博士研究生，研究方向为生物固碳及固碳酶。E-mail：zhaolei191@mails.ucas.ac.cn。
基金资助:
国家重点研发计划(2021YFC2103502);天津市合成生物技术创新能力提升行动项目(TSBICIP-KJGG-006-19)

Research progress of formic acid biotransformation

ZHAO Tongxin¹(), ZHAO Lei¹^,²(), ZHANG Yanping¹(), LI Yin¹

^1.CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China
^2.University of Chinese Academy of Sciences, Beijing 100049, China

Received:2022-08-22 Revised:2022-09-24 Online:2023-01-25 Published:2023-02-20
Contact: ZHANG Yanping

摘要/Abstract

摘要：

“碳达峰、碳中和”是我国提出的重要战略目标。到2060年，在保持我国经济中高速增长的前提下，要实现生产、生活等各类活动排放的二氧化碳等温室气体，与生物固定转化及其他技术固存的二氧化碳量互相抵消，即“排放”与“吸收利用”达到平衡，挑战巨大。如何开展二氧化碳的高效减排、捕集和利用，促进双碳目标的实现，已经成为科研界和产业界共同关注的重大课题和迫切任务。目前已发现6条天然的固碳途径，但普遍存在固碳效率低、改造困难等问题。近年来，随着电化学技术的发展，二氧化碳化学转化为甲酸的技术已日渐成熟，以甲酸为底物的生物转化成为生物固碳领域的热点研究方向。本文系统总结近年来在甲酸生物转化途径改造和重构，与之匹配的还原力供给方式以及甲酸自养型菌株构建等方面的最新研究进展，并探讨甲酸生物转化中的主要问题和突破方向。

关键词: 甲酸, 生物固碳, 能量供给, 甲酸自养菌, 代谢途径

Abstract:

The vision of attaining a carbon peak and achieving carbon neutrality guides the transition to a low-carbon economic system in China. It is a huge challenge to achieve by 2060, under the premise of continuing the high-speed economic growth, that the quantity of carbon dioxide and other greenhouse gases emitted by diverse activities such as production and living might be offset by the amount of carbon dioxide sequestered by bio-fixation-transformation and other technologies. How to balance "emission" and "absorption and utilization," as well as carry out effective emission reduction, capture and reuse of carbon dioxide to promote the achievement of carbon peaking and carbon neutrality goals, has emerged as a critical issue and pressing task for scientific study and industrial development. To date, six natural CO₂ fixation pathways have been identified, although there are problems such as poor carbon efficiency and challenging modification. With the development of electrochemical technology, the chemical conversion of carbon dioxide to formic acid has become increasingly mature in recent years. Biotransformation using formic acid as a substrate has become a popular issue in biological carbon fixation. In this review, we summarize the latest research progress in the transformation and reconstruction of formic acid biotransformation pathway, mainly emphasizing on the reducing power balancing and the construction of formic acid autotrophic strains, and also discuss the existed problems of formic acid biotransformation and its potential breakthroughs.

Key words: formate, carbon fixation pathway, energy supply, autotrophic organisms, metabolic pathway

中图分类号:

赵同心, 赵磊, 张延平, 李寅. 甲酸微生物转化研究进展[J]. 化工进展, 2023, 42(1): 67-72.

ZHAO Tongxin, ZHAO Lei, ZHANG Yanping, LI Yin. Research progress of formic acid biotransformation[J]. Chemical Industry and Engineering Progress, 2023, 42(1): 67-72.

图/表 2

图1 甲酸同化途径灰色色块为上游甲酸同化共有模块；蓝色线条指示途径为亚甲基四氢叶酸-甘氨酸-丝氨酸-丙酮酸线性途径；绿色途径为天然亚甲基四氢叶酸-丝氨酸循环；红色途径为亚甲基四氢叶酸-改良丝氨酸循环；黄色途径为亚甲基四氢叶酸-苏氨酸/丝氨酸循环。循环产物分别为乙酰辅酶A（浅绿色块）或丙酮酸（天蓝色块）

表1 关于甲酸生物转化的大肠杆菌分子改造研究进展

途径	基因型	主要结果	参考文献
甲酸→甘氨酸→丝氨酸	MG1655∆serA∆ltaE∆kbl∆aceA pZSSM: ftfL, fch, mtdA, glyA	葡萄糖、甲酸、10%CO₂共培养条件下，能够回补丝氨酸和甘氨酸缺陷型菌株生长	[11]
甲酸→甘氨酸→丝氨酸→丙酮酸	JCL16∆serA PsdaA::P_LlacO1 P_LtetO1: fhs_Cl, fchA_Cl, folD_Cl P_LlacO1: gcvTHP	葡萄糖、¹³C-甲酸、HCO $3 -$ 共培养条件下，并未检测到丙酮酸，但检测到¹³C标记的丙氨酸	[10]
甲酸→甘氨酸→丝氨酸→丙酮酸	DH5αΔgcvRΔpflBΔserAPgcvTHP::P_Ltrc p10099a BBa23100: ftfL, fch, mtdA BBa23100: gcvTHP, lpd	葡萄糖、¹³C甲酸、¹³CO₂共培养，甲酸线性路径贡献丙酮酸合成代谢流的14.9%	[9]
丝氨酸/苏氨酸循环	MG1655ΔserAΔgcvTHP pZ vector P_pgimutant: glyA, sdaA, folD, tdh, kbl, ftfL	葡萄糖、甲酸共培养，能够支撑菌株生长所需的甘氨酸和丝氨酸	[12]
改良的丝氨酸循环	“甘氨酸+甲酸→丙酮酸→草酰乙酸”模块： BL21(DE3)ΔaceAΔgcvP sdaA(C. n), fthfI(M. t), mthfs(M. t)	乙酸、甘氨酸、甲酸共培养，菌株能够缓慢生长	[13]
改良的丝氨酸循环	“丙酮酸→草酰乙酸→丝氨酸”模块： BL21(DE3)ΔserAΔgcvP mtk(M. c), mcl(M. e), AGX1(S. c), fthfI(M. t), mthfs(M. t),medh(CT4-1), faldh(P. p)	丙酮酸、甲醇共培养，菌株能够缓慢生长	[13]

表1 关于甲酸生物转化的大肠杆菌分子改造研究进展

途径	基因型	主要结果	参考文献
甲酸→甘氨酸→丝氨酸	MG1655∆serA∆ltaE∆kbl∆aceA pZSSM: ftfL, fch, mtdA, glyA	葡萄糖、甲酸、10%CO₂共培养条件下，能够回补丝氨酸和甘氨酸缺陷型菌株生长	[11]
甲酸→甘氨酸→丝氨酸→丙酮酸	JCL16∆serA PsdaA::P_LlacO1 P_LtetO1: fhs_Cl, fchA_Cl, folD_Cl P_LlacO1: gcvTHP	葡萄糖、¹³C-甲酸、HCO $3 -$ 共培养条件下，并未检测到丙酮酸，但检测到¹³C标记的丙氨酸	[10]
甲酸→甘氨酸→丝氨酸→丙酮酸	DH5αΔgcvRΔpflBΔserAPgcvTHP::P_Ltrc p10099a BBa23100: ftfL, fch, mtdA BBa23100: gcvTHP, lpd	葡萄糖、¹³C甲酸、¹³CO₂共培养，甲酸线性路径贡献丙酮酸合成代谢流的14.9%	[9]
丝氨酸/苏氨酸循环	MG1655ΔserAΔgcvTHP pZ vector P_pgimutant: glyA, sdaA, folD, tdh, kbl, ftfL	葡萄糖、甲酸共培养，能够支撑菌株生长所需的甘氨酸和丝氨酸	[12]
改良的丝氨酸循环	“甘氨酸+甲酸→丙酮酸→草酰乙酸”模块： BL21(DE3)ΔaceAΔgcvP sdaA(C. n), fthfI(M. t), mthfs(M. t)	乙酸、甘氨酸、甲酸共培养，菌株能够缓慢生长	[13]
改良的丝氨酸循环	“丙酮酸→草酰乙酸→丝氨酸”模块： BL21(DE3)ΔserAΔgcvP mtk(M. c), mcl(M. e), AGX1(S. c), fthfI(M. t), mthfs(M. t),medh(CT4-1), faldh(P. p)	丙酮酸、甲醇共培养，菌株能够缓慢生长	[13]

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甲酸微生物转化研究进展

Research progress of formic acid biotransformation

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