High-level production of Tauroursodeoxycholic acid from Taurochenodeoxycholic acid in engineered Bacillus subtilis via whole-cell biotransformation.

Lina Jin, Tengfei Niu, Rufeng Wang, Li Yang, Shujuan Zhao, Zhengtao Wang

Abstract read

In one paragraph

Article in World journal of microbiology & biotechnology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

6 authors.

Lina JinThe SATCM Key Laboratory for New Resources & Quality Evaluation of Chinese Medicine, Shanghai Key Laboratory of Compound Chinese Medicines, State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Institute of Chinese Materia Medica, The MOE Key Laboratory for Standardization of Chinese Medicines, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, P.R. China.

Tengfei NiuThe SATCM Key Laboratory for New Resources & Quality Evaluation of Chinese Medicine, Shanghai Key Laboratory of Compound Chinese Medicines, State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Institute of Chinese Materia Medica, The MOE Key Laboratory for Standardization of Chinese Medicines, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, P.R. China.

Rufeng WangThe SATCM Key Laboratory for New Resources & Quality Evaluation of Chinese Medicine, Shanghai Key Laboratory of Compound Chinese Medicines, State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Institute of Chinese Materia Medica, The MOE Key Laboratory for Standardization of Chinese Medicines, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, P.R. China.

Li YangThe SATCM Key Laboratory for New Resources & Quality Evaluation of Chinese Medicine, Shanghai Key Laboratory of Compound Chinese Medicines, State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Institute of Chinese Materia Medica, The MOE Key Laboratory for Standardization of Chinese Medicines, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, P.R. China.

Shujuan ZhaoThe SATCM Key Laboratory for New Resources & Quality Evaluation of Chinese Medicine, Shanghai Key Laboratory of Compound Chinese Medicines, State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Institute of Chinese Materia Medica, The MOE Key Laboratory for Standardization of Chinese Medicines, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, P.R. China. zhaoshujuan@126.com.ORCID http://orcid.org/0000-0002-2269-925X

Zhengtao WangThe SATCM Key Laboratory for New Resources & Quality Evaluation of Chinese Medicine, Shanghai Key Laboratory of Compound Chinese Medicines, State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Institute of Chinese Materia Medica, The MOE Key Laboratory for Standardization of Chinese Medicines, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, P.R. China.

Funding

Natural Science Foundation of Shanghai 21ZR1463000Shanghai Science and Technology Development Fund from Central Leading Local Government YDZX20223100001004

6 · The paper itself

Abstract

Bear bile powder, a valuable traditional Chinese medicinal material, is distinguished by its high content of tauroursodeoxycholic acid (TUDCA), typically present at a ratio of 0.82 to 1.76 relative to taurochenodeoxycholic acid (TCDCA). In this study, the generally recognized as safe (GRAS) bacterium Bacillus subtilis was engineered to create a two-step enzymatic pathway for TCDCA to TUDCA bioconversion, utilizing bidirectional redox enzymes 7α/7β-hydroxysteroid dehydrogenase. Ribosome binding site (RBS) optimization and glucose 1-dehydrogenase (GDH)-mediated NAD(P)H cofactor regeneration were implemented to increase TUDCA production. The engineered strains A2-2 and A2-2-5 produced 15.10 ± 0.36 g/L and 14.33 ± 1.24 g/L of TUDCA, with TUDCA/TCDCA ratios of 1.22 and 0.88, respectively, following 15 h of fermentation in a whole-cell biocatalytic system. T-7-KLCA intermediate was undetectable. This study provided a cost-effective and scalable approach for the industrial production of potential bear bile substitutes from readily available chicken bile powder using an engineered probiotic B. subtilis microbial cell factory.

Indexed as

Bacillus subtilisMetabolic EngineeringTaurochenodeoxycholic AcidAnimalsBiotransformationFermentationGlucose 1-DehydrogenaseHydroxysteroid DehydrogenasesUrsidae7 alpha-hydroxysteroid dehydrogenase7 beta-hydroxysteroid dehydrogenaseGlucose 1-DehydrogenaseHydroxysteroid DehydrogenasesTaurochenodeoxycholic AcidursodoxicoltaurineBacillus subtilisBear bile powderChicken bile powderNAD(P)H cofactor regenerationRibosome-binding siteTauroursodeoxycholic acid

Identifiers

PMID40999182

DOI10.1007/s11274-025-04549-7

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.