Non-toxic antimicrobial peptide Hm-AMP2 from leech metagenome proteins identified by the gradient-boosting approach

作     者：Grafskaia, Ekaterina N. Pavlova, Elizaveta R. Latsis, Ivan A. Malakhova, Maja V. Ivchenkov, Dmitrii V. Bashkirov, Pavel V. Kot, Erik F. Mineev, Konstantin S. Arseniev, Alexander S. Klinov, Dmitry V. Lazarev, Vassili N. 

作者机构：Fed Med Biol Agcy Fed Res & Clin Ctr Phys Chem Med Moscow 119435 Russia Russian Acad Sci Shemyakin Ovchinnikov Inst Bioorgan Chem Moscow 117997 Russia Natl Res Univ Moscow Inst Phys & Technol 141700 Dolgoprudny Moscow 141701 Russia Peoples Friendship Univ Russia RUDN Univ Moscow 117198 Russia 

出 版 物：《MATERIALS & DESIGN》 (Mater. Des.)

年 卷 期：2022年第224卷

核心收录：

学科分类：08[工学] 0805[工学-材料科学与工程（可授工学、理学学位）] 080502[工学-材料学] 

基　　金：Russian Science Foundation [20-15-00270] 

主　　题：Antimicrobial peptides Medicinal leech Non-toxic effect Gradient boosting algorithm 

摘      要：The number of infections caused by antibiotic-resistant pathogens is increasing alarmingly every year and will continue to grow. Antimicrobial peptides (AMPs) are considered new therapeutic agents for the effective combat against infectious diseases. We report the design of antimicrobial peptides derived from a database of leech metagenome proteins using a machine learning approach. Peptides with antimicrobial activity and reduced toxicity were identified by the CatBoost algorithm. Among them, Hm-AMP2 possesses the most promising application in practice, including antibacterial activity against both Gram-positive and Gram-negative bacteria, low cytotoxic and hemolytic effects. Hm-AMP2 kills various bacteria at low concentrations (4.6-18.5 lM) by the disruption of bacterial membranes. According to nuclear magnetic resonance analysis, the peptide adopts an a-helical structure in a membrane environment. Hm-AMP2 interacts with lipopolysaccharides of different bacteria according to microscale thermophoresis and CD spectroscopy analysis. This effect can play a role in the first defense against the organism s bacterial invasion. The computational approach developed for the identification of AMP can be useful for the rational design of effective non-toxic peptide antibiotics. (c) 2022 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-NDlicense (http://***/licenses/by-nc-nd/4.0/).