Chemo-enzymatic total synthesis: current approaches toward the integration of chemical and enzymatic transformations

• Ryo Tanifuji and
• Hiroki Oguri

Beilstein J. Org. Chem. 2024, 20, 1693–1712, doi:10.3762/bjoc.20.151

• , efficiency, and robustness of these biocatalysts are expected to enhance their usefulness and generality as synthetic tools. Apart from oxygenated terpenes and RiPPs, chemo-enzymatic approaches for polyketides and non-ribosomal peptides (NRPs) are considered more suitable for the second and third strategies

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

• -translational modifications; ribosomal peptides; SAM-dependent enzymes; Introduction In the complex landscape of natural product biosynthesis, ribosomally synthesised and post-translationally modified peptides (RiPPs) stand out as a fascinating class of compounds with both structural diversity and unique

• ; this reaction is catalysed by S-adenosylmethionine (SAM or AdoMet)-dependent methyltransferases (MTs). These enzymes are known for their excellent chemo-, regio-, and stereoselectivity [3][4][5][6]. Their ability to introduce methyl groups at specific positions within ribosomal peptides equips the

• can also be employed to mimic non-ribosomal peptides [12][13], since it is substantially more challenging to engineer non-ribosomal peptide synthetase (NRPS) pathways. Non-ribosomal peptides are often produced by giant multi-modular enzyme complexes (type I NRPS) and they are most commonly involved in

Optimizations of lipid II synthesis: an essential glycolipid precursor in bacterial cell wall synthesis and a validated antibiotic target

• Milandip Karak,
• Cian R. Cloonan,
• Brad R. Baker,
• Rachel V. K. Cochrane and
• Stephen A. Cochrane

Beilstein J. Org. Chem. 2024, 20, 220–227, doi:10.3762/bjoc.20.22

• ramoplanin [2]. It is also the target for a host of other antimicrobials (mostly non-ribosomal peptides), including the tridecaptins [3], nisin [4], teixobactin [5], clovibactin [6], malacidin [7], and cilagicin [8]. Despite significant progress in the chemical synthesis of lipid II and its analogues, the

Tenacibactins K–M, cytotoxic siderophores from a coral-associated gliding bacterium of the genus Tenacibaculum

• Yasuhiro Igarashi,
• Yiwei Ge,
• Tao Zhou,
• Amit Raj Sharma,
• Enjuro Harunari,
• Naoya Oku and
• Agus Trianto

Beilstein J. Org. Chem. 2022, 18, 110–119, doi:10.3762/bjoc.18.12

• from 2.5 to 7.9 Mbp, biosynthetic gene clusters for siderophores, terpenes, and non-ribosomal peptides were identified by genome mining [39], suggesting a high capability of secondary metabolism in this genus. Further investigation is underway to disclose the actual diversity of metabolites from the

Natural products in the predatory defence of the filamentous fungal pathogen Aspergillus fumigatus

• Jana M. Boysen,
• Nauman Saeed and
• Falk Hillmann

Beilstein J. Org. Chem. 2021, 17, 1814–1827, doi:10.3762/bjoc.17.124

• ; non-ribosomal peptides; polyketides; secondary metabolism; virulence; Introduction To thrive in their natural habitats all organisms from bacteria and fungi to plants and animals need access to sufficient nutritional sources and have to defend themselves against both, competitors and predators

• molecules like non-ribosomal peptides (NRP), polyketides (PK), terpenes or indole alkaloids [10][11]. The vast majority of fungal BGCs is found in the genomes of members of the Basidiomycota and Ascomycota including the genus Penicillium in which the first BGC was identified in 1990 [12][13][14

¹⁹F NMR as a tool in chemical biology

• Diana Gimenez,
• Aoife Phelan,
• Cormac D. Murphy and
• Steven L. Cobb

Beilstein J. Org. Chem. 2021, 17, 293–318, doi:10.3762/bjoc.17.28

• the detection of the new compounds in the complex supernatants of organisms producing non-ribosomal peptides and polyketides. It has been especially useful for monitoring the incorporation

A cyclopeptide and three oligomycin-class polyketides produced by an underexplored actinomycete of the genus Pseudosporangium

• Shun Saito,
• Kota Atsumi,
• Tao Zhou,
• Keisuke Fukaya,
• Daisuke Urabe,
• Naoya Oku,
• Md. Rokon Ul Karim,
• Hisayuki Komaki and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 1100–1110, doi:10.3762/bjoc.16.97

• DSM 45348, using the AntiSMASH database [17], and identified in total 14 biosynthetic gene clusters for polyketides and non-ribosomal peptides. Intrigued by this, a strain available from the NBRC culture collections [18] was cultured and examined by HPLC–DAD analysis, which gave several peaks in the

Synthesis and SAR of the antistaphylococcal natural product nematophin from Xenorhabdus nematophila

• Frank Wesche,
• Hélène Adihou,
• Thomas A. Wichelhaus and
• Helge B. Bode

Beilstein J. Org. Chem. 2019, 15, 535–541, doi:10.3762/bjoc.15.47

• pathogenic against humans, they are widely used as biocontrol agents in agriculture [9]. Natural products produced by bacteria play an important role in the bacteria/nematode/insect life cycle and most natural products are non-ribosomal peptides (NRP), e.g., rhabdopeptides [10][11] and polyketide–NRP hybrids

From chemical metabolism to life: the origin of the genetic coding process

• Antoine Danchin

Beilstein J. Org. Chem. 2017, 13, 1119–1135, doi:10.3762/bjoc.13.111

• , essential for compartmentalisation [29]), a variety of (iso)peptides as in the synthesis of fatty acids today, non-ribosomal peptides and polyketides [30]. The involvement of thioesters in a primitive metabolism, predating the systematic input of phosphate has been documented by Segré and co-workers in a

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

• hydrolysis and disulphide bond formation through to the complex remodelling of almost every amino acid in a molecule. For example, thiopeptide antibiotics [15] and the marine toxin polytheonamide [16] were both believed to be non-ribosomal peptides for a number of years, while the bacterial cofactor

• predictably than molecules made from multi-domain megasynthases such as polyketides and non-ribosomal peptides. Cyclisation is a common post-translational modification in RiPP pathways and includes a multitude of transformations. These modifications are usually essential for the proper biological activity of

• highly similar, and is distinct from their generation in non-ribosomal peptides. The first in vitro reconstitution of a TOMM was carried out with microcin B17 [28][32][33], which showed that there are four essential proteins for its biosynthesis: the precursor peptide (the “A” protein McbA) that is post

Marine-derived myxobacteria of the suborder Nannocystineae: An underexplored source of structurally intriguing and biologically active metabolites

• Antonio Dávila-Céspedes,
• Peter Hufendiek,
• Max Crüsemann,
• Till F. Schäberle and
• Gabriele M. König

Beilstein J. Org. Chem. 2016, 12, 969–984, doi:10.3762/bjoc.12.96

• metabolites can be found in various detailed reports [19][20][21][22][23]. The majority of these metabolites are either non-ribosomal peptides, e.g., cystobactamids 1–3 (Figure 1) [24], polyketides, e.g., aurafuron A (4) [25], or hybrids thereof, e.g., corallopyronin A (5, Figure 2) [26]. Interestingly, an

• gene clusters, among them three NRPS, two PKS, three NRPS/PKS and four ribosomal peptides (see Table 1). Apart from homologies to geosmin (100%), aurafuron (71%) and paneibactin (50%) biosynthetic genes, the gene clusters display a large degree of novelty. Recently, the biosynthetic gene cluster of

Recent highlights in biosynthesis research using stable isotopes

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2015, 11, 2493–2508, doi:10.3762/bjoc.11.271

• classes including polyketides, non-ribosomal peptides, their hybrids, terpenoids, and aromatic compounds formed via the shikimate pathway. The text does not aim at a comprehensive overview, but instead a selection of recent important examples of isotope usage within biosynthetic studies is presented, with

• ], but these aspects will not be discussed here. Instead, this review highlights recent biosynthetic studies using isotopes from major classes of natural products including polyketides, non-ribosomal peptides, hybrids thereof, isoprenoids and a few aromatic compounds that arise via the shikimate pathway

• -ribosomal peptides Non-ribosomal peptides often exhibit a high bioactivity and are biosynthesized by non-ribosomal peptide synthethases (NRPS) [33], which work RNA-independent and catalyze the assembly of both proteinogenic and non-proteinogenic amino acids in a modular fashion. Moreover, NRPSs can contain

Natural product biosyntheses in cyanobacteria: A treasure trove of unique enzymes

• Jan-Christoph Kehr,
• Douglas Gatte Picchi and
• Elke Dittmann

Beilstein J. Org. Chem. 2011, 7, 1622–1635, doi:10.3762/bjoc.7.191

• obtained from the biochemical studies of cyanobacterial pathways can inspire the development of concepts for the design of bioactive compounds by synthetic-biology approaches in the future. Keywords: cyanobacteria; natural products; NRPS; PKS; ribosomal peptides; Introduction The role of cyanobacteria in