微生物中一碳代谢网络构建的进展与挑战

doi:10.12211/2096-8280.2021-079

合成生物学 ›› 2022, Vol. 3 ›› Issue (1): 116-137.doi: 10.12211/2096-8280.2021-079

微生物中一碳代谢网络构建的进展与挑战

郭姝媛^1,², 吴良焕^1,², 刘香健^1,², 王博^1,², 于涛^1,²

^1.中国科学院深圳先进技术研究院，深圳合成生物学创新研究院，合成生物化学研究中心，广东深圳 518055
^2.中国科学院深圳先进技术研究院，深圳合成生物学创新研究院，中国科学院定量工程生物学重点实验室，广东深圳 518055

收稿日期:2021-07-23 修回日期:2021-10-21 出版日期:2022-02-28 发布日期:2022-03-14
通讯作者: 于涛
作者简介:郭姝媛（1991—），女，博士，博士后。主要从事基于酿酒酵母的甲醇生物转化及产物合成研究。E-mail：sy.guo@siat.ac.cn|于涛（1986—），男，博士，研究员。主要从事酿酒酵母的合成生物学研究。E-mail：tao.yu@siat.ac.cn
基金资助:
中国博士后科学基金(2020M682973);国家重点研发计划(2020YFA0907800);国家自然科学基金(32071416);广东省基础与应用基础研究基金(2020A1515110927);深圳合成生物学创新研究院项目(JCHZ20200003)

Developing C₁-based metabolic network in methylotrophy for biotransformation

Shuyuan GUO^1,², Lianghuan WU^1,², Xiangjian LIU^1,², Bo WANG^1,², Tao YU^1,²

^1.Center for Synthetic Biochemistry，Shenzhen Institute of Synthetic Biology，Shenzhen Institutes of Advanced Technology，Chinese Academy of Sciences，Shenzhen 518055，Guangdong，China
^2.CAS Key Laboratory of Quantitative Engineering Biology，Shenzhen Institute of Synthetic Biology，Shenzhen Institutes of Advanced Technology，Chinese Academy of Sciences，Shenzhen 518055，Guangdong，China

Received:2021-07-23 Revised:2021-10-21 Online:2022-02-28 Published:2022-03-14
Contact: Tao YU

摘要/Abstract

摘要：

利用来源广、价格低、易制备且储量丰富的一碳化合物作为底物，通过构建甲基营养型细胞工厂，生物合成多种高附加值化学品，不仅可以促进一碳资源的洁净利用，同时可以缓解能源短缺、环境污染等问题。因此，深入了解甲基营养型微生物（天然型和合成型）的一碳代谢网络，是高效利用一碳化合物进行生物炼制的关键。本文综述了多种一碳化合物（甲烷、甲醇、甲酸和二氧化碳）生物炼制的研究进展，主要包括两个部分：（1）甲基营养型微生物（天然型和合成型）的关键代谢酶及多种代谢网络；（2）基于多种甲基营养型微生物进行生物合成的研究现状。文章最后讨论了一碳化合物作为底物进行生物转化所面临的主要瓶颈，并据此提供可行的研究策略，以期推动一碳化合物作为原材料进行生物炼制的工业化进程。

关键词: 甲基营养型微生物, 一碳代谢, 一碳化合物, 生物转化, 代谢工程

Abstract:

One carbon (C₁) substrates have generated increasing attention as abundantly available feedstock for biotransformation to produce biofuels and valuable chemicals. Especially, these bioproducts are not only promoting the economic development, but also meet the societal needs for clean energy and environmental protection. Microbial cell factories (MCF) that efficiently convert raw materials to useful chemicals are highly desirable for C1 based biomanufacturing. Furthermore, more and more attention is being paid to study how the native and synthetic methylotrophic MCFs are capable of utilizing C1 compounds including methane, methanol, formic acid and carbon dioxide (CO₂) as raw materials for biosynthesis. Native methylotrophs have multiple pathways for C₁ utilization so that they can grow with methanol or formate as the sole carbon and energy source. Engineering synthetic methylotrophs are based on available metabolic knowledge and advanced genome engineering tools to modify the platform microorganisms. Hence, it is the key to explore the C₁-based metabolic networks of methylotrophy in depth for constructing highly effective methylotrophic cell factory to convert C₁ substrates. In this review, we firstly summarize in detail key natural pathways for C₁-substrate assimilation and bioproducts produced by native methylotrophs. Then we introduce synthetic methylotrophs and major chemical products derived through engineering Escherichia coli, Corynebacterium glutamicum and Saccharomyces cerevisiae. In the field of synthetic methylotrophs, many studies focus on utilizing methanol or CO₂ as the sole carbon source and energy source to construct the MCFs for bio-transformation. In the end, we discuss the barriers and challenges for developing robust methylotrophic cell factory to convert C₁ substrates, and highlight strategies for commercializing the biotransformation of C₁ based substrates.

Key words: methylotrophs, one-carbon metabolism, C₁ compounds, biotransformation, metabolic engineering

中图分类号:

Q 815

郭姝媛, 吴良焕, 刘香健, 王博, 于涛. 微生物中一碳代谢网络构建的进展与挑战[J]. 合成生物学, 2022, 3(1): 116-137, doi: 10.12211/2096-8280.2021-079.

Shuyuan GUO, Lianghuan WU, Xiangjian LIU, Bo WANG, Tao YU. Developing C₁-based metabolic network in methylotrophy for biotransformation[J]. Synthetic Biology Journal, 2022, 3(1): 116-137, doi: 10.12211/2096-8280.2021-079.

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微生物中一碳代谢网络构建的进展与挑战

Developing C₁-based metabolic network in methylotrophy for biotransformation

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微生物中一碳代谢网络构建的进展与挑战

Developing C1-based metabolic network in methylotrophy for biotransformation

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Developing C₁-based metabolic network in methylotrophy for biotransformation