2. Academic Validation
  3. Identification of gut microbial bile acid metabolic enzymes via an AI-assisted pipeline

Identification of gut microbial bile acid metabolic enzymes via an AI-assisted pipeline

  • Cell. 2025 Jul 31:S0092-8674(25)00806-2. doi: 10.1016/j.cell.2025.07.017.
Yong Ding 1,  Xi Luo 2,  Jiasheng Guo 3,  Baiying Xing 4,  Haoyu Lin 5,  Haohan Ma 2,  Yicun Wang 2,  Meng Li 2,  Chuan Ye 2,  Sen Yan 6,  Kangjie Lin 3,  Jinxin Zhang 2,  Yingying Zhuo 2,  Qixing Nie 7,  Donghui Yang 4,  Zhipeng Zhang 8,  Yanli Pang 6,  Kai Wang 9,  Ming Ma 10,  Luhua Lai 11,  Changtao Jiang 12
Affiliations

Affiliations

  • 1 Department of Immunology, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing 100191, China; NHC Key Laboratory of Medical Immunology, Peking University, Beijing, China.
  • 2 Department of Physiology and Pathophysiology, Center for Obesity and Metabolic Disease Research, School of Basic Medical Sciences, Peking University, Beijing 100191, China.
  • 3 Center for Life Sciences at BNLMS, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
  • 4 State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
  • 5 Center for Quantitative Biology, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China.
  • 6 Institute of Advanced Clinical Medicine, State Key Laboratory of Female Fertility Promotion, Center for Reproductive Medicine, Third Hospital, Peking University, Beijing, China; National Clinical Research Center for Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China; Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, China.
  • 7 State Key Laboratory of Food Science and Resources, Key Laboratory of Bioactive Polysaccharides of Jiangxi Province, Nanchang University, Nanchang, China.
  • 8 Department of General Surgery, Peking University Third Hospital, Beijing, China.
  • 9 Department of Immunology, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing 100191, China; NHC Key Laboratory of Medical Immunology, Peking University, Beijing, China. Electronic address: wangkai@bjmu.edu.cn.
  • 10 State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China. Electronic address: mma@bjmu.edu.cn.
  • 11 Center for Life Sciences at BNLMS, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China; Center for Quantitative Biology, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China; Peking University Chengdu Academy for Advanced Interdisciplinary Biotechnologies, Chengdu 510100, Sichuan, China. Electronic address: lhlai@pku.edu.cn.
  • 12 Department of Immunology, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing 100191, China; NHC Key Laboratory of Medical Immunology, Peking University, Beijing, China; Institute of Advanced Clinical Medicine, State Key Laboratory of Female Fertility Promotion, Center for Reproductive Medicine, Third Hospital, Peking University, Beijing, China; Center of Basic Medical Research, Institute of Medical Innovation and Research, Peking University Third Hospital, Beijing, China. Electronic address: jiangchangtao@bjmu.edu.cn.
PMID: 40780197 DOI: 10.1016/j.cell.2025.07.017
Abstract

The modifications of bile acids (BAs) are fundamental to their role in host physiology and pathology. Identifying their synthetases is crucial for uncovering the diversity of BAs and developing targeted interventions, yet it remains a significant challenge. To address this hurdle, we developed an artificial intelligence (AI)-assisted workflow, bile acid enzyme announcer unit tool (BEAUT), which predicted over 600,000 candidate BA metabolic Enzymes that we compiled into the human generalized microbial BA metabolic enzyme (HGBME) database (https://beaut.bjmu.edu.cn). We identified a series of uncharacterized BA Enzymes, including monoacid acylated BA hydrolase (MABH) and 3-acetoDCA synthetase (ADS). Notably, ADS can produce an unreported skeleton BA, 3-acetoDCA, with a carbon-carbon bond extension. After determining its Bacterial source and catalytic mechanism, we found that 3-acetoDCA is widely distributed among populations and regulates the microbial interactions in the gut. In conclusion, our work offers alternative insights into the relationship between microbial BAs and the host from an enzymatic perspective.

Keywords

3-acetoDCA; ADS; MABH; artificial intelligence; bile acid; biosynthesis enzyme; gut microbiota.

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