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Rapidly directional biotransformation of tauroursodeoxycholic acid through engineered Escherichia coli

  • Metabolic Engineering and Synthetic Biology - Original Paper
  • Published:
Journal of Industrial Microbiology & Biotechnology

Abstract

Bear bile powder is a precious medicinal material. It is characterized by high content of tauroursodeoxycholic acid (TUDCA) at a ratio of 1.0–1.5 to taurochenodeoxycholic acid (TCDCA). Here, we reported the biotransformation of tauroursodeoxycholic acid (TUDCA) through Escherichia coli engineered with a two-step mimic biosynthetic pathway of TUDCA from taurochenodeoxycholic acid (TCDCA). Two 7α-hydroxysteroid dehydrogenase (7α-HSDH) and two 7β-hydroxysteroid dehydrogenase (7β-HSDH) genes (named as α1, α2, β1, and β2) were selected and synthesized to create four pathway variants using ePathBrick. All could convert TCDCA to TUDCA and the one harboring α1 and β2 (pα1β2) showed the strongest capability. Utilizing the oxidative and reductive properties of 7α- and 7β-HSDH, an ideal balance between TUDCA and TCDCA was established by optimizing the fermentation conditions. By applying the optimal condition, E. coli containing pα1β2 (BL-pα1β2) produced up to 1.61 ± 0.13 g/L of TUDCA from 3.23 g/L of TCDCA at a ratio of 1.3 to TCDCA. This study provides a potential approach for bear bile substitute production from cheap and readily available chicken bile.

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Acknowledgements

This study was funded by the National Science and Technology Major Projects (2014ZX09301306-007) and National Science Foundation of China (No. 81673540). We greatly appreciate Professor Zhibi Hu and Mrs Jiyan Zhou, Shanghai University of Traditional Chinese Medicine, for their valuable comments and suggestions, and the company of Shanghai Kaibao Pharmaceutica Co. Ltd., China for providing chicken bile and the standard reference of bile acids.

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Authors and Affiliations

  1. The SATCM Key Laboratory for New Resources & Quality Evaluation of Chinese Medicine, The MOE Key Laboratory for Standardization of Chinese Medicines and Shanghai Key Laboratory of Complex Prescription, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China

    Jie Shi, Jie Wang, Lu Yu, Li Yang, Shujuan Zhao & Zhengtao Wang

  2. Department of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, 110016, China

    Lu Yu

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  1. Jie Shi
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  2. Jie Wang
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  3. Lu Yu
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  4. Li Yang
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  5. Shujuan Zhao
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  6. Zhengtao Wang
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Correspondence to Shujuan Zhao or Zhengtao Wang.

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Shi, J., Wang, J., Yu, L. et al. Rapidly directional biotransformation of tauroursodeoxycholic acid through engineered Escherichia coli . J Ind Microbiol Biotechnol 44, 1073–1082 (2017). https://doi.org/10.1007/s10295-017-1935-y

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  • DOI: https://doi.org/10.1007/s10295-017-1935-y

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