Unveiling the evolution of antimicrobial peptides in gut microbes via foundation-model-powered framework
Summary: Antimicrobial resistance poses a major threat to public health, prompting the development of alternative therapies such as antimicrobial peptides (AMPs). Protein language models (PLMs) have advanced protein structure and function predictions, facilitating AMP discovery. We developed antimic...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-06-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124725005443 |
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| author | Wenhui Li Baicheng Huang Menghao Guo Zihan Zeng Tao Cai Linqing Feng Xinpeng Zhang Ling Guo Xianyue Jiang Yanbin Yin Ercheng Wang Xingxu Huang Jinfang Zheng |
| author_facet | Wenhui Li Baicheng Huang Menghao Guo Zihan Zeng Tao Cai Linqing Feng Xinpeng Zhang Ling Guo Xianyue Jiang Yanbin Yin Ercheng Wang Xingxu Huang Jinfang Zheng |
| author_sort | Wenhui Li |
| collection | DOAJ |
| description | Summary: Antimicrobial resistance poses a major threat to public health, prompting the development of alternative therapies such as antimicrobial peptides (AMPs). Protein language models (PLMs) have advanced protein structure and function predictions, facilitating AMP discovery. We developed antimicrobial peptide structural evolution miner (AMP-SEMiner), an AI-driven framework that integrates PLMs, structural clustering, and evolutionary analysis to systematically identify AMPs encoded by small open reading frames and AMP-containing proteins in metagenome-assembled genomes. AMP-SEMiner identified over 1.6 million AMP candidates across diverse environments. Experimental validation showed antimicrobial activity in 9 of the 20 tested candidates, with 5 surpassing antibiotic effectiveness; variant peptides derived from these candidates similarly demonstrated strong antimicrobial efficacy. AMPs from human gut microbiomes revealed both conserved and adaptive evolutionary strategies, reflecting their dynamic ecological roles. AMP-SEMiner thus represents a valuable tool for expanding AMP discovery and has significant potential to inform the development of alternative antimicrobial treatments. |
| format | Article |
| id | doaj-art-cadcfae4afad4bf3bb434676d3bb6ec9 |
| institution | DOAJ |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-cadcfae4afad4bf3bb434676d3bb6ec92025-08-20T03:21:51ZengElsevierCell Reports2211-12472025-06-0144611577310.1016/j.celrep.2025.115773Unveiling the evolution of antimicrobial peptides in gut microbes via foundation-model-powered frameworkWenhui Li0Baicheng Huang1Menghao Guo2Zihan Zeng3Tao Cai4Linqing Feng5Xinpeng Zhang6Ling Guo7Xianyue Jiang8Yanbin Yin9Ercheng Wang10Xingxu Huang11Jinfang Zheng12Research Center for Life Sciences Computing, Zhejiang Lab, Hangzhou, Zhejiang 311121, China; School of Life Sciences and Technology, Tongji University, Shanghai 200092, ChinaResearch Center for Life Sciences Computing, Zhejiang Lab, Hangzhou, Zhejiang 311121, ChinaResearch Center for Life Sciences Computing, Zhejiang Lab, Hangzhou, Zhejiang 311121, ChinaResearch Center for Life Sciences Computing, Zhejiang Lab, Hangzhou, Zhejiang 311121, ChinaResearch Center for Life Sciences Computing, Zhejiang Lab, Hangzhou, Zhejiang 311121, ChinaResearch Center for Life Sciences Computing, Zhejiang Lab, Hangzhou, Zhejiang 311121, ChinaNebraska Food for Health Center, Department of Food Science and Technology, University of Nebraska, Lincoln, NE 68588, USAResearch Center for Life Sciences Computing, Zhejiang Lab, Hangzhou, Zhejiang 311121, ChinaResearch Center for Life Sciences Computing, Zhejiang Lab, Hangzhou, Zhejiang 311121, ChinaNebraska Food for Health Center, Department of Food Science and Technology, University of Nebraska, Lincoln, NE 68588, USAResearch Center for Life Sciences Computing, Zhejiang Lab, Hangzhou, Zhejiang 311121, China; Corresponding authorZhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou 311121, China; School of Life Science and Technology, ShanghaiTech University, Shanghai 200092, China; Corresponding authorResearch Center for Life Sciences Computing, Zhejiang Lab, Hangzhou, Zhejiang 311121, China; Corresponding authorSummary: Antimicrobial resistance poses a major threat to public health, prompting the development of alternative therapies such as antimicrobial peptides (AMPs). Protein language models (PLMs) have advanced protein structure and function predictions, facilitating AMP discovery. We developed antimicrobial peptide structural evolution miner (AMP-SEMiner), an AI-driven framework that integrates PLMs, structural clustering, and evolutionary analysis to systematically identify AMPs encoded by small open reading frames and AMP-containing proteins in metagenome-assembled genomes. AMP-SEMiner identified over 1.6 million AMP candidates across diverse environments. Experimental validation showed antimicrobial activity in 9 of the 20 tested candidates, with 5 surpassing antibiotic effectiveness; variant peptides derived from these candidates similarly demonstrated strong antimicrobial efficacy. AMPs from human gut microbiomes revealed both conserved and adaptive evolutionary strategies, reflecting their dynamic ecological roles. AMP-SEMiner thus represents a valuable tool for expanding AMP discovery and has significant potential to inform the development of alternative antimicrobial treatments.http://www.sciencedirect.com/science/article/pii/S2211124725005443CP: Microbiology |
| spellingShingle | Wenhui Li Baicheng Huang Menghao Guo Zihan Zeng Tao Cai Linqing Feng Xinpeng Zhang Ling Guo Xianyue Jiang Yanbin Yin Ercheng Wang Xingxu Huang Jinfang Zheng Unveiling the evolution of antimicrobial peptides in gut microbes via foundation-model-powered framework Cell Reports CP: Microbiology |
| title | Unveiling the evolution of antimicrobial peptides in gut microbes via foundation-model-powered framework |
| title_full | Unveiling the evolution of antimicrobial peptides in gut microbes via foundation-model-powered framework |
| title_fullStr | Unveiling the evolution of antimicrobial peptides in gut microbes via foundation-model-powered framework |
| title_full_unstemmed | Unveiling the evolution of antimicrobial peptides in gut microbes via foundation-model-powered framework |
| title_short | Unveiling the evolution of antimicrobial peptides in gut microbes via foundation-model-powered framework |
| title_sort | unveiling the evolution of antimicrobial peptides in gut microbes via foundation model powered framework |
| topic | CP: Microbiology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124725005443 |
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