Discovery of antimicrobial peptides clostrisin and cellulosin from Clostridium: insights into their structures, co-localized biosynthetic gene clusters, and antibiotic activity
Moisés Alejandro Alejo Hernandez, Katia Pamela Villavicencio Sánchez, Rosendo Sánchez Morales, Karla Georgina Hernández-Magro Gil, David Silverio Moreno-Gutiérrez, Eddie Guillermo Sanchez-Rueda, Yanet Teresa-Cruz, Brian Choi, Armando Hernández Garcia, Alba Romero-Rodríguez, Oscar Juárez, Siseth Martínez-Caballero, Mario Figueroa, Corina-Diana Ceapă
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引用次数: 0
Abstract
Antimicrobial resistance presents a substantial threat to global public health, demanding urgent attention and action. This study focuses on lanthipeptides, ribosomally encoded peptides that display significant structural diversity and hold promising potential as antibiotics. Genome mining was employed to locate biosynthetic gene clusters (BGCs) containing class II lanthipeptide synthetases encoded by lanM genes. A phylogenetic study analyzing homologous sequences of functional LanM sequences revealed a unique evolutionary clade of 17 LanM proteins associated with 12 Clostridium bacterial genomes. In silico exploration identified nine complete BGCs, including one super-cluster containing two co-localized operons from Clostridium cellulovorans 743B, that encode for two new peptides named clostrisin and cellulosin. Each operon was heterologously expressed in Escherichia coli. Molecular weights associated with the expected post-translational modifications of the purified lanthipeptide were confirmed by MS–MS/MS analysis for cellulosin, while clostrisin was not post-translationally modified. Both peptides demonstrated antimicrobial activity against multidrug-resistant bacteria, such as a clinical strain of Staphylococcus epidermidis MIQ43 and Pseudomonas aeruginosa PA14. This is the first report of lanthipeptides from the Clostridium genus produced with its native biosynthetic machinery, as well as chemically and biologically characterized. This study showcases the immense potential of genome mining in identifying new RiPP synthetases and associated bioactive peptides.
Beilstein J. Org. Chem.2024,20, 1800–1816. doi:10.3762/bjoc.20.159
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The Beilstein Journal of Organic Chemistry is an international, peer-reviewed, Open Access journal. It provides a unique platform for rapid publication without any charges (free for author and reader) – Platinum Open Access. The content is freely accessible 365 days a year to any user worldwide. Articles are available online immediately upon publication and are publicly archived in all major repositories. In addition, it provides a platform for publishing thematic issues (theme-based collections of articles) on topical issues in organic chemistry.
The journal publishes high quality research and reviews in all areas of organic chemistry, including organic synthesis, organic reactions, natural product chemistry, structural investigations, supramolecular chemistry and chemical biology.
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