Unveiling the Evolution of Antimicrobial Peptides in Gut Microbes via Foundation Model-Powered Framework

doi:10.1101/2025.01.13.632881

	Unveiling the Evolution of Antimicrobial Peptides in Gut Microbes via Foundation Model-Powered Framework
	Li, Wenhui 1,2; Huang, Baicheng 1; Guo, Menghao 1; Zeng, Zihan 1; Cai, Tao 1; Feng, Linqing 1; Zhang, Xinpeng 3; Guo, Ling 1; Jiang, Xianyue 1; Yin, Yanbin 3; Wang, Ercheng 1; Huang, Xingxu4,5,6 ; Zheng, Jinfang Zheng 1
	2025-01-13
状态	已发表
摘要	Antimicrobial resistance poses a growing threat to public health, emphasizing the urgent need for novel therapeutic strategies. Antimicrobial peptides (AMPs), short peptide sequences with diverse mechanisms of action, offer a promising alternative due to their broad-spectrum activity against pathogens. Recent advances in protein language models (PLMs) have revolutionized protein structure prediction and functional annotation, highlighting their potential for AMP discovery and therapeutic development. In this context, we present AMP-SEMiner (Antimicrobial Peptide Structural Evolution Miner), an AI-driven framework designed to identify AMPs from metagenome-assembled genomes (MAGs). By integrating PLMs, structural clustering and evolutionary analysis into the framework, AMP-SEMiner can identify AMPs encoded by small open reading frames (smORFs) and encrypted peptides (EPs), significantly expanding the discovery space. Using this approach, we identified 1,670,600 AMP candidates from diverse habitats. Experimental validation of 29 candidates revealed antimicrobial activity in 18, with 13 surpassing antibiotics in effectiveness. Further analysis of AMPs from human gut microbiomes demonstrated both conserved and adaptive evolutionary strategies, ensuring their functional efficacy in the dynamic gut environment. These findings position AMP-SEMiner as a powerful tool for the discovery and characterization of novel AMPs, with significant potential to drive the development of new antimicrobial therapies.
语种	英语
DOI	10.1101/2025.01.13.632881
相关网址	查看原文
出处	bioRxiv
收录类别	PPRN.PPRN
WOS记录号	PPRN:120514730
WOS类目	Microbiology
资助项目	National Natural Science Foundation of China[82450113] ; Pioneer and "Leading Goose" R&D Program of Zhejiang[2024SSYS0007]
文献类型	预印本
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/496892
专题	生命科学与技术学院生命科学与技术学院_PI研究组_黄行许组
通讯作者	Wang, Ercheng; Huang, Xingxu; Zheng, Jinfang Zheng
作者单位	1.Zhejiang Lab, Res Ctr Life Sci Comp, Hangzhou 311121, Zhejiang, Peoples R China 2.Tongji Univ, Sch Life Sci & Technol, Shanghai 200092, Peoples R China 3.Univ Nebraska, Nebraska Food Hlth Ctr, Dept Food Sci & Technol, Lincoln, NE 68588, USA 4.Zhejiang Univ, Affiliated Hosp 1, Sch Med, Zhejiang Prov Key Lab Pancreat Dis, Hangzhou 311121, Peoples R China 5.Zhejiang Univ, Inst Translat Med, Sch Med, Hangzhou 311121, Peoples R China 6.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 200092, Peoples R China
推荐引用方式 GB/T 7714	Li, Wenhui,Huang, Baicheng,Guo, Menghao,et al. Unveiling the Evolution of Antimicrobial Peptides in Gut Microbes via Foundation Model-Powered Framework. 2025.