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Recent advances in n-butanol and butyrate production using engineered Clostridium tyrobutyricum

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Abstract

Acidogenic clostridia naturally producing acetic and butyric acids has attracted high interest as a novel host for butyrate and n-butanol production. Among them, Clostridium tyrobutyricum is a hyper butyrate-producing bacterium, which re-assimilates acetate for butyrate biosynthesis by butyryl-CoA/acetate CoA transferase (CoAT), rather than the phosphotransbutyrylase-butyrate kinase (PTB-BK) pathway widely found in clostridia and other microbial species. To date, C. tyrobutyricum has been engineered to overexpress a heterologous alcohol/aldehyde dehydrogenase, which converts butyryl-CoA to n-butanol. Compared to conventional solventogenic clostridia, which produce acetone, ethanol, and butanol in a biphasic fermentation process, the engineered C. tyrobutyricum with a high metabolic flux toward butyryl-CoA produced n-butanol at a high yield of > 0.30 g/g and titer of > 20 g/L in glucose fermentation. With no acetone production and a high C4/C2 ratio, butanol was the only major fermentation product by the recombinant C. tyrobutyricum, allowing simplified downstream processing for product purification. In this review, novel metabolic engineering strategies to improve n-butanol and butyrate production by C. tyrobutyricum from various substrates, including glucose, xylose, galactose, sucrose, and cellulosic hydrolysates containing the mixture of glucose and xylose, are discussed. Compared to other recombinant hosts such as Clostridium acetobutylicum and Escherichia coli, the engineered C. tyrobutyricum strains with higher butyrate and butanol titers, yields and productivities are the most promising hosts for potential industrial applications.

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Acknowledgments

Some of the authors’ work described in this review was supported by the National Science Foundation STTR program (IIP-0810568, IIP-1026648) and Ohio Department of Development—Third Frontier Advanced Energy Program (Tech 08-036).

Funding

Some of the work described in this review paper was supported by the National Science Foundation STTR program (IIP-0810568, IIP-1026648), Ohio Department of Development—Third Frontier Advanced Energy Program (Tech 08-036).

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Author notes

  1. Teng Bao and Jun Feng have contributed equally to this work.

Authors and Affiliations

  1. Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, OH, 43210, USA

    Teng Bao, Wenyan Jiang & Shang-Tian Yang

  2. School of Biology and Biological Engineering, South China University of Technology, Guangzhou, 510006, China

    Jun Feng, Hongxin Fu & Jufang Wang

Authors
  1. Teng Bao
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  2. Jun Feng
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  3. Wenyan Jiang
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  4. Hongxin Fu
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  5. Jufang Wang
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  6. Shang-Tian Yang
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Contributions

STY had the idea for the article. TB, JF, WJ, and HF performed the literature search and data analysis. BT and JF each drafted different sections of the paper. JW and STY critically revised the work.

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Correspondence to Shang-Tian Yang.

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Bao, T., Feng, J., Jiang, W. et al. Recent advances in n-butanol and butyrate production using engineered Clostridium tyrobutyricum. World J Microbiol Biotechnol 36, 138 (2020). https://doi.org/10.1007/s11274-020-02914-2

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