甲基杆菌有效同化工业甲醇和植物甲醇的研究进展

doi:10.16085/j.issn.1000-6613.2024-1841

化工进展 ›› 2025, Vol. 44 ›› Issue (5): 2451-2462.DOI: 10.16085/j.issn.1000-6613.2024-1841

• 合成生物制造 • 上一篇

甲基杆菌有效同化工业甲醇和植物甲醇的研究进展

姚陆¹^,²^,³(), 马增新¹^,²^,³(), 张聪¹^,²^,³, 杨松¹^,²^,³(), 邢新会⁴^,⁵()

^1.青岛农业大学生命科学学院，山东青岛 266109
^2.青岛农业大学山东省应用真菌重点实验室，山东青岛 266109
^3.青岛农业大学青岛生物沼气环境微生物国际合作基地，山东青岛 266109
^4.清华大学工业生物催化教育部重点实验室，化工系生物化工研究所，合成与系统生物学中心，北京 100084
^5.清华大学深圳国际研究生院生物医药与健康工程研究院，广东深圳 518055

收稿日期:2024-11-11 修回日期:2025-02-10 出版日期:2025-05-25 发布日期:2025-05-20
通讯作者: 杨松,邢新会
作者简介:姚陆（1990—），男，博士，研究方向为代谢工程和微生物菌剂。E-mail：yaolu113@163.com
马增新（1988—），男，博士，研究方向为代谢工程和合成生物学。E-mail：mazengxin@foxmail.com。
基金资助:
国家重点研发计划(2021YFC2103500);国家自然科学基金(22078169);国家自然科学基金青年基金(31900004)

Recent advances in strengthening Methylobacterium chassis for the utilization of methanol from industrial and plant sources

YAO Lu¹^,²^,³(), MA Zengxin¹^,²^,³(), ZHANG Cong¹^,²^,³, YANG Song¹^,²^,³(), XING Xinhui⁴^,⁵()

^1.School of Life Sciences, Qingdao Agricultural University, Qingdao 266109, Shandong, China
^2.Shandong Province Key Laboratory of Applied Mycology, Qingdao Agricultural University, Qingdao 266109, Shandong, China
^3.Qingdao International Center on Microbes Utilizing Biogas, Qingdao Agricultural University, Qingdao 266109, Shandong, China
^4.MOE Key Laboratory for Industrial Biocatalysis, Institute of Biochemical Engineering, Department of Chemical Engineering, Center for Synthetic & Systems Biology, Tsinghua University, Beijing 100084, China
^5.Institute of Biopharmaceutical and Health Engineering, Tsinghua Shenzhen International Graduate School, Shenzhen 518055, Guangdong, China

Received:2024-11-11 Revised:2025-02-10 Online:2025-05-25 Published:2025-05-20
Contact: YANG Song, XING Xinhui

摘要/Abstract

摘要：

甲醇是第三代工业生物制造的重要原料，同时又能伴随植物生长排放到大气中加剧温室效应。甲基杆菌是一类能以甲醇作为生长碳源和能源的极具广泛应用前景的菌株。然而甲基杆菌催化转化高浓度工业甲醇和寡浓度植物甲醇的过程效率偏低，导致甲醇的碳和电子耗散，制约了甲醇的高值化利用。本文首先系统综述了甲基杆菌底盘再造强化工业甲醇有效代谢方面的最新策略，进而论述了甲基杆菌对植物源寡浓度甲醇有效氧化、同化和转化的最新认知，最后展望了甲基杆菌进一步强化甲醇利用的可行性研究方向与策略。本综述期望推动甲基杆菌作为甲醇基细胞工厂和新型植物益生菌剂的技术创新，助力工业生物制造的甲醇高值化，增强植物甲醇的固定封存，实现经济与生态环境效益的共赢发展。

关键词: 甲基杆菌, 甲醇, 甲基细胞工厂, 植物叶际益生菌, 合成生物技术

Abstract:

Methanol is a significant raw material for third-generation industrial biomanufacturing and is also released into the atmosphere during plant growth, contributing to the greenhouse effect. Methylobacterium is a type of strain with broad application prospects and can use methanol as a carbon source and energy for growth. However, the catalytic conversion process of high-concentration industrial methanol and low-concentration plant methanol by Methylobacterium exhibits low efficiency, which results in the unnecessary dissipation of methanol's carbon and electrons, thereby limiting the high-value utilization of methanol. This article presents a systematic review of the latest strategies for enhancing the effective metabolism of industrial methanol through chassis remodeling of Methylobacterium. It subsequently discusses current insights into Methylobacterium's effective oxidation, assimilation, and conversion of low-concentration methanol derived from plant sources. Finally, this review explores potential research directions and strategies for further enhancing methanol utilization by Methylobacterium. Its objectives include promoting scientific research and technology innovation on Methylobacterium as a methanol-based cellular factory and a novel plant probiotic agent. This supports the high-value utilization of methanol in industrial biotechnology, enhances the fixation and sequestration of plant-derived methanol, and aims to achieve a win-win solution strategy for both economic and eco environmental benefits.

Key words: Methylobacterium, methanol, methylotrophic cell factory, plant phyllospheric probiotics, synthetic biotechnology

中图分类号:

姚陆, 马增新, 张聪, 杨松, 邢新会. 甲基杆菌有效同化工业甲醇和植物甲醇的研究进展[J]. 化工进展, 2025, 44(5): 2451-2462.

YAO Lu, MA Zengxin, ZHANG Cong, YANG Song, XING Xinhui. Recent advances in strengthening Methylobacterium chassis for the utilization of methanol from industrial and plant sources[J]. Chemical Industry and Engineering Progress, 2025, 44(5): 2451-2462.

图/表 4

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产品	代谢工程策略	发酵规模	产量	参考文献
单细胞蛋白	高密度发酵	发酵罐	42~72g/L	[16-17]
聚β-羟基丁酸酯	限氮两阶段发酵	发酵罐	46~136g/L	[18-19]
聚β-羟基丁酸-戊酸-己酸酯	替换本源phaC，过表达β-酮硫解酶和乙酰乙酰辅酶A还原酶	摇瓶	43.6%	[20]
衣康酸	表达顺乌头酸脱羧酶，并解除PhaR调控	摇瓶	31.6mg/L	[21]
异丁醇	优化异丁醇合成途径基因及拷贝，减少竞争途径乳酸合成	摇瓶	19mg/L	[11]
3-羟基丙酸	表达mcr并优化启动子和拷贝数	摇瓶	69.8mg/L	[22]
3-羟基丙酸	构建协同同化途径，强化ATP和还原力供给	发酵罐	0.86g/L	[23]
3-羟基丙酸	构建光合甲基营养型菌株，强化能量供给	发酵罐	1.8g/L	[24]
蛇麻烯	表达甲羟戊酸途径和蛇麻烯合酶	发酵罐	1.65g/L	[25]
甲羟戊酸	构建甲羟戊酸生物传感器对转录因子QscR进行筛选	发酵罐	2.67g/L	[26]
2-羟基异丁酸	筛选3-羟基丁酰辅酶A变位酶并进行限氮两阶段发酵	发酵罐	2.1g/L	[27]
类胡萝卜素	利用CRISPRi打靶竞争途径	摇瓶	0.3μg/mg	[28]
紫色杆菌素	表达紫色杆菌素基因簇vioABCDE并进行随机突变筛选	摇瓶	118mg/L	[29]

产品	代谢工程策略	发酵规模	产量	参考文献
单细胞蛋白	高密度发酵	发酵罐	42~72g/L	[16-17]
聚β-羟基丁酸酯	限氮两阶段发酵	发酵罐	46~136g/L	[18-19]
聚β-羟基丁酸-戊酸-己酸酯	替换本源phaC，过表达β-酮硫解酶和乙酰乙酰辅酶A还原酶	摇瓶	43.6%	[20]
衣康酸	表达顺乌头酸脱羧酶，并解除PhaR调控	摇瓶	31.6mg/L	[21]
异丁醇	优化异丁醇合成途径基因及拷贝，减少竞争途径乳酸合成	摇瓶	19mg/L	[11]
3-羟基丙酸	表达mcr并优化启动子和拷贝数	摇瓶	69.8mg/L	[22]
3-羟基丙酸	构建协同同化途径，强化ATP和还原力供给	发酵罐	0.86g/L	[23]
3-羟基丙酸	构建光合甲基营养型菌株，强化能量供给	发酵罐	1.8g/L	[24]
蛇麻烯	表达甲羟戊酸途径和蛇麻烯合酶	发酵罐	1.65g/L	[25]
甲羟戊酸	构建甲羟戊酸生物传感器对转录因子QscR进行筛选	发酵罐	2.67g/L	[26]
2-羟基异丁酸	筛选3-羟基丁酰辅酶A变位酶并进行限氮两阶段发酵	发酵罐	2.1g/L	[27]
类胡萝卜素	利用CRISPRi打靶竞争途径	摇瓶	0.3μg/mg	[28]
紫色杆菌素	表达紫色杆菌素基因簇vioABCDE并进行随机突变筛选	摇瓶	118mg/L	[29]

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[11]	龙涛, 周锋, 张伟, 吴泓, 王建, 陈霖. CO-CO₂体系制备氘代甲醇催化剂的合成与改性[J]. 化工进展, 2024, 43(8): 4411-4420.
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[14]	周运桃, 王洪星, 李新刚, 崔丽凤. CeO₂载体在CO₂加氢制甲醇中的应用和研究进展[J]. 化工进展, 2024, 43(5): 2723-2738.
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甲基杆菌有效同化工业甲醇和植物甲醇的研究进展

Recent advances in strengthening Methylobacterium chassis for the utilization of methanol from industrial and plant sources

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