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 and
• Corina-Diana Ceapă

Beilstein J. Org. Chem. 2024, 20, 1800–1816, doi:10.3762/bjoc.20.159

• 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

• 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. Keywords: antimicrobials; genome mining; lantibiotics; lanthipeptides; multi-drug resistant bacteria; natural products; Introduction Antimicrobial resistance (AMR) is a significant public health challenge. Only in 2019, there were 4.95 million deaths associated with AMR [1

Methyltransferases from RiPP pathways: shaping the landscape of natural product chemistry

• Maria-Paula Schröder,
• Isabel P.-M. Pfeiffer and
• Silja Mordhorst

Beilstein J. Org. Chem. 2024, 20, 1652–1670, doi:10.3762/bjoc.20.147

• Lachnospiraceae bacterium C6A11. It belongs structurally to class I MTs and was the first MT observed acting on the C-terminus of lanthipeptides. Furthermore, it is the second occurrence of an O-MT acting on lanthipeptides, alongside the LanSA-type O-MTs [71]. LahSB methylates four out of seven LahA precursor

Cyclisation mechanisms in the biosynthesis of ribosomally synthesised and post-translationally modified peptides

• Andrew W. Truman

Beilstein J. Org. Chem. 2016, 12, 1250–1268, doi:10.3762/bjoc.12.120

• for a number of characterised secondary metabolite pathways. For example, the bottromycin gene cluster encodes two stand-alone YcaO domain proteins that have been postulated to participate in heterocyclisation reactions [10][11][12][13]. Lanthionine bond formation in lanthipeptides Lanthipeptides

• suppresses bacterial spoilage. Lanthipeptides are characterised by meso-lanthionine (Lan) and (2S,3S,6R)-3-methyllanthionine (MeLan) residues. Lanthionine consist of two alanine residues linked via a thioether that connects their β-carbons, while MeLan contains an additional methyl group (Figure 4B). These

• residues [47][48][49]. Lanthipeptides are divided into four distinct classes (I–IV) based on the differences between the biosynthetic enzymes that carry out dehydration and cyclisation [44]. Dehydration in class I lanthipeptide pathways is catalysed by a LanB dehydratase (NisB for nisin) and cyclisation is