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

• 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

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

• within the context of ribosomally synthesised and post-translationally modified peptide (RiPP) natural products. Methyltransferases play a pivotal role in the biosynthesis of diverse natural products with unique chemical structures and bioactivities. They are highly chemo-, regio-, and stereoselective

• other bioactive compounds. By providing an overview of the various methylation options available, this review is intended to emphasise the biocatalytic potential of RiPP methyltransferases and their impact on the field of natural product chemistry. Keywords: biocatalysis; methylation; post

• bioactivities [1]. RiPP natural products are typically encoded in a biosynthetic gene cluster (BGC) and produced following defined biosynthetic rules. Initially, a precursor peptide encompassing a core peptide, a leader part and/or a follower part, is synthesised at the ribosome. Next, distinct maturases

Mining raw plant transcriptomic data for new cyclopeptide alkaloids

• Draco Kriger,
• Michael A. Pasquale,
• Brigitte G. Ampolini and
• Jonathan R. Chekan

Beilstein J. Org. Chem. 2024, 20, 1548–1559, doi:10.3762/bjoc.20.138

• and post-translationally modified peptide (RiPP) natural products offer a valuable opportunity for bioinformatics-guided discovery in plants due to their short biosynthetic pathways and gene encoded substrates. Using a high-throughput approach to assemble and analyze 700 publicly available raw

• prevalent in plants [4]. Like all known plant peptides, burpitides fall under the ribosomally synthesized and post-translationally modified peptides (RiPPs) superclass of natural products (Figure 1). The typical pathway for a RiPP starts with a precursor peptide made by the ribosome that undergoes post

• biosynthetic enzymes. Ultimately proteolysis releases the modified core peptide as the mature RiPP natural product [5][6]. In the case of the newly described burpitide family of RiPPs, the defining feature is the presence of amino acid side-chain crosslinks installed by a copper-dependent burpitide cyclase [4

Chemical and biosynthetic potential of Penicillium shentong XL-F41

• Ran Zou,
• Xin Li,
• Xiaochen Chen,
• Yue-Wei Guo and
• Baofu Xu

Beilstein J. Org. Chem. 2024, 20, 597–606, doi:10.3762/bjoc.20.52

• version of antiSMASH 7.0 [25] software for the analysis of the Penicillium shentong XL-F41 genome, we identified 46 BGCs. These include 13 NRPS-like fragments, 6 NRPS, 13 type I PKS, 2 PKS/NRPS hybrids, 1 NI-siderophore, 2 NRP-metallophore/NRPS hybrids, 1 fungal RiPP with POP or UstH peptidase types, 1

• fungal-RiPP-like/T1PKS, 1 betalactone, 1 PKS type I/NRPS/indole hybrid, 1 fungal-RiPP-like/T1PKS hybrid, 1 NRP-metallophore/NRPS hybrid, NRPS-like/terpene/phosphonate hybrids, 3 terpenes, and 1 indole-related cluster (Table 5). BGC 7.3, identified as an indole-type gene cluster, includes genes for

Navigating and expanding the roadmap of natural product genome mining tools

• Friederike Biermann,
• Sebastian L. Wenski and
• Eric J. N. Helfrich

Beilstein J. Org. Chem. 2022, 18, 1656–1671, doi:10.3762/bjoc.18.178

• combination of all genome mining approaches will pave the way towards a more comprehensive understanding of the full biosynthetic repertoire encoded in microbial genome sequences. Keywords: genome mining; natural product biosynthesis; non-canonical pathways; PKS; NRPS; RiPP; Introduction In 2002, the genome

• ])) [28]. In contrast, discrete multi-enzymatic assemblies utilize distinct, monofunctional enzymes. Examples are terpene (e.g., cyclooctatin (8) [29]), ribosomally synthesized and post-translationally modified peptide (RiPP), or NRPS-independent alkaloid pathways. In the case of terpene biosynthesis

• conserved across all 40 plus RiPP families [32]. However, each RiPP BGC family features genes encoding characteristic tailoring enzymes, or precursor peptides, that show a high degree of sequence conservation within the family. These conserved genes can be utilized for the targeted, family-specific

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

• amount of RiPP chemical diversity is generated from cyclisation reactions, and the current mechanistic understanding of these reactions will be discussed here. These cyclisations involve a diverse array of chemical reactions, including 1,4-nucleophilic additions, [4 + 2] cycloadditions, ATP-dependent

• heterocyclisation to form thiazolines or oxazolines, and radical-mediated reactions between unactivated carbons. Future prospects for RiPP pathway discovery and characterisation will also be highlighted. Keywords: biosynthesis; cyclisation; enzymes; peptides; RiPPs; Introduction Nature employs a number of routes

• RiPP pathways, which are often small and lacking in homology to one another [9]. There has therefore been a massive increase in the study of their biosynthesis in recent years. RiPPs usually originate from a larger precursor peptide that consists of an N-terminal leader sequence and a core peptide that