北京大学姜长涛课题组报道了通过人工智能辅助管道鉴定肠道微生物胆汁酸代谢酶。相关论文发表在2025年8月7日出版的《细胞》杂志上。
为了解决这个问题，研究组开发了一个人工智能（AI）辅助的工作流程，胆汁酸酶播音员单元工具（BEAUT），该工具预测了超过60万种候选BA代谢酶，并将其编译到人类通用微生物BA代谢酶（HGBME）数据库（https://beaut.bjmu.edu.cn）中。该研究团队鉴定了一系列未被鉴定的BA酶，包括单酸酰化BA水解酶（MABH）和3-乙酰DCA合成酶（ADS）。值得注意的是，ADS可以产生未报道的骨架BA， 3-acetoDCA，具有碳-碳键延伸。通过对3-acetoDCA的细菌存在和催化机制的测定，研究团队发现3-acetoDCA广泛分布于人群中，并调节肠道内微生物的相互作用。总之，他们的工作从酶的角度为微生物BAs和宿主之间的关系提供了另一种见解。
据悉，胆汁酸（BAs）的修饰是其在宿主生理和病理中的作用的基础。确定它们的合成酶对于揭示BAs的多样性和开发有针对性的干预措施至关重要，但这仍然是一个重大挑战。
附：英文原文
Title: Identification of gut microbial bile acid metabolicenzymes via an AI-assisted pipeline
Author: Yong Ding, Xi Luo, Jiasheng Guo, Baiying Xing, Haoyu Lin, Haohan Ma, Yicun Wang, Meng Li, Chuan Ye, Sen Yan, Kangjie Lin, Jinxin Zhang, Yingying Zhuo, Qixing Nie, Donghui Yang, Zhipeng Zhang, Yanli Pang, Kai Wang, Ming Ma, Luhua Lai, Changtao Jiang
Issue&Volume: 2025-08-07
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.
DOI: 10.1016/j.cell.2025.07.017
Source: https://www.cell.com/cell/abstract/S0092-8674(25)00806-2