Genome Mining Reveals the Structure of the Clostrisin and Cellulosin Biosynthetic Gene Clusters, Two Novel Lantibiotics

Submitting author affiliation:
UNAM, CDMX, Mexico

Beilstein Arch. 2023, 202356.

Published 06 Dec 2023

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This preprint has not been peer-reviewed. When a peer-reviewed version is available, this information will be updated.


Antimicrobial resistance is an issue of enormous proportions that poses a significant threat to global public health. This study focuses on lanthipeptides, ribosomally encoded peptides which display significant structural diversity and hold promising potential as antibiotics. Genome mining was employed to locate biosynthetic gene clusters (BGC) for class II lanthipeptides. A phylogenetic study analyzing homologous sequences of functional LanM sequences revealed a unique evolutionary clade of 39 LanMs associated with 28 Clostridial bacterial genomes. In silico exploration identified nine complete BGCs, including one from Clostridium cellulovorans 743B, that harbors two new lanthipeptides: Clostrisin and Cellulosin. The lanthipeptide BGCs were heterologously expressed in Escherichia coli. Molecular weights associated with the expected post-translational modifications of the purified lanthipeptides were confirmed by MALDI-TOF. Both peptides demonstrated antimicrobial activity against multidrug-resistant bacteria, such as a clinical strain of Staphylococcus epidermidis MIQ43 and a reference strain of resistant Pseudomonas aeruginosa PA14. This study showcases the immense potential of genome mining in identifying new class II lanthipeptides.

Keywords: Antimicrobials, multi-drug resistant bacteria, natural products, Clostridium sp.

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When a peer-reviewed version of this preprint is available, this information will be updated in the information box above. If no peer-reviewed version is available, please cite this preprint using the following information:

Alejo Hernandez, M. A.; Villavicencio Sánchez, K. P.; Sánchez Morales, R.; Hernández-Magro Gil, K. G.; Moreno-Gutiérrez, D. S.; Sanchez-Rueda, E. G.; Teresa-Cruz, Y.; Hernández Garcia, A.; Romero-Rodríguez, A.; Juárez, O.; Martínez-Caballero, S.; Figueroa, M.; Ceapa, C. D. Beilstein Arch. 2023, 202356. doi:10.3762/bxiv.2023.56.v1

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