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Production of bilirubin by biotransformation of biliverdin using recombinant Escherichia coli cells

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Abstract

Bilirubin, a natural intermediate in heme degradation, is a valuable Chinese medicine used in more than 50 traditional Chinese medicine (TCM) preparations. At present, bilirubin is mainly produced by extraction from pig bile, but a shortage of the raw material has increased the price, to about US$10,000/kg in the Chinese market. Biliverdin, the precursor of bilirubin, is more abundant and less expensive than bilirubin, but it is not used in TCM. Thus, the biotransformation of biliverdin by biliverdin reductase (BvdR) may be a practical way to produce bilirubin. In this study, the codon-optimized gene of biliverdin reductase (mbvdR) from the cyanobacterium Synechocystis was cloned into Escherichia coli BL21(DE3), and the conditions for BL21-mBvdR expressing BvdR were optimized. Resting BL21-mBvdR cells were employed as biocatalysts to biotransform biliverdin to bilirubin. At a concentration of biliverdin substrate of 450 mg/L in the reaction mixture, the bilirubin content in dry cells reached 20.8 ± 0.8 mg/g, with a conversion yield of 72.3%. Therefore, recombinant E. coli expressing BvdR can be applied to biotransform biliverdin to bilirubin, providing a potential alternative process for bilirubin production.

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Acknowledgements

This research was financially supported by Shanghai Hebutong Technology Co., Ltd. and the Science and Technology Department of Zhejiang Province (Grant No. 2021C03088).

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Authors and Affiliations

  1. College of Pharmaceutical Science, Zhejiang University of Technology, 18 Chaowang Road, Gongshu District, Hangzhou, 310014, People’s Republic of China

    Jianfeng Mei, Xia Wu, Sujing Zheng, Yu Yi, Xudong Wang & Guoqing Ying

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  1. Jianfeng Mei
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  2. Xia Wu
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  3. Sujing Zheng
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  4. Yu Yi
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  5. Xudong Wang
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  6. Guoqing Ying
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Contributions

JM: conceptualization, methodology, and writing (review and editing) XW: investigation, methodology, and writing (original draft preparation). SZ: investigation. YY: methodology and validation. XW: resources and validation. GY: project administration.

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Correspondence to Guoqing Ying.

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Mei, J., Wu, X., Zheng, S. et al. Production of bilirubin by biotransformation of biliverdin using recombinant Escherichia coli cells. Bioprocess Biosyst Eng 45, 563–571 (2022). https://doi.org/10.1007/s00449-021-02679-4

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  • DOI: https://doi.org/10.1007/s00449-021-02679-4

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