Abstract：
The study aimed to mine and characterize novel antimicrobial peptides (AMPs) from the Shanxi aged vinegar microbiome. Utilizing machine learning techniques, AlphaFold2 structure prediction and molecular dynamics simulations, six novel AMPs were innovatively mined from 98,539 peptides based on metagenomic data, of which one peptide secreted by Lactobacillus (named La-AMP) was experimentally validated to have remarkable bactericidal effects against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) with high stability and no hemolytic activity. Scanning electron microscopy revealed that La-AMP caused irreversible damage to cell membranes of S. aureus and E. coli, a finding further confirmed by calcein-AM/propidium iodide staining. Additionally, La-AMP induced nucleic acid leakage and reactive oxygen species accumulation in bacterial cells. It was found to bind to DNA gyrase through salt bridges, hydrogen bonds, and hydrophobic interactions, ultimately inducing apoptosis. Thus, La-AMP exhibited encouraging promise as a valuable bioactive component for the development of natural preservatives.
摘要：
该研究旨在从山西老陈醋微生物组中挖掘和表征新型抗菌肽（AMPs）。利用机器学习技术，AlphaFold2结构预测和分子动力学模拟，基于宏基因组数据，从98,539个肽中创新性地开采了6个新的AMP，其中一种由乳杆菌分泌的肽（名为La-AMP）经实验验证对金黄色葡萄球菌具有显着的杀菌作用（S.金黄色葡萄球菌)和大肠杆菌(E.coli)稳定性高,无溶血活性。扫描电镜显示La-AMP对金黄色葡萄球菌和大肠杆菌的细胞膜造成不可逆的损伤,钙黄绿素-AM/碘化丙啶染色进一步证实了这一发现。此外,La-AMP诱导细菌细胞中的核酸泄漏和活性氧积累。发现它通过盐桥与DNA促旋酶结合，氢键,和疏水相互作用，最终诱导细胞凋亡。因此，La-AMP作为开发天然防腐剂的有价值的生物活性成分表现出令人鼓舞的前景。
