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Recent progress in metabolic engineering of microbial formate assimilation

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Abstract

Formate can be efficiently produced via electrochemical or photochemical catalytic conversion of CO2, and it can be directly used as an organic carbon source by microorganisms. In theory, formate can be used as the sole carbon source for the microbial production of high-value-added chemicals. Consequently, the construction of efficient formate-assimilation pathways in microorganisms is essential for the utilization of cheap, renewable one-carbon compounds. This paper summarizes new methods of formate synthesis, as well as the natural formate utilization pathways of microorganisms with their advantages and disadvantages. Furthermore, it reviews recent progress in the design of utilization pathways for formate in microbial cells through metabolic engineering and synthetic biology. Besides, we also use the pathway-prediction algorithm comb-FBA to rationally design completely new one-carbon compounds utilization pathways. The pathway with the highest efficiency, named GAA, was corroborated by the in vitro experiments showing a carbon molar yield up to 88%. Finally, it discusses the main problems and challenges presently existing in the pathway design and strain improvement for microbial utilization of formate.

Key points

• Natural and artificial design pathways of formate-assimilation was summarized.

• Recent progresses in different hosts and approaches of using one-carbon compounds was reviewed.

• Metabolic engineering and synthetic biology methods to improve formate utilization were discussed.

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Funding

This work was financially supported by the National Key Research and Development Program of China (2018YFA0900200) and National Natural Science Foundation of China (NSFC-21621004, NSFC-21908239).

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Author notes

  1. Wen Mao and Qianqian Yuan contributed equally to this work.

Authors and Affiliations

  1. Frontier Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering (Ministry of Education); SynBio Research Platform, Collaborative Innovation Center of Chemical Science and Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300072, China

    Wen Mao, Zhiwen Wang & Tao Chen

  2. Key Laboratory of Systems Microbial Biotechnology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, 300308, China

    Qianqian Yuan & Hongwu Ma

  3. Yantai Justaware Pharmaceutical CO., Ltd., Fuan Pharmaceutical Group, Yantai, 264000, China

    Hongge Qi

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  1. Wen Mao
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  4. Zhiwen Wang
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Contributions

Mao W and Yuan Qq studied, summed up the relative literatures, and wrote the manuscript. Qi Hg provided the frame and the research goal of article. Wang Zw and Ma Hw were responsible for proofreading and reviewed article. Chen T revised the manuscript and supervised this work. All authors read and approved the manuscript.

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Correspondence to Tao Chen.

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Mao, W., Yuan, Q., Qi, H. et al. Recent progress in metabolic engineering of microbial formate assimilation. Appl Microbiol Biotechnol 104, 6905–6917 (2020). https://doi.org/10.1007/s00253-020-10725-6

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