Extension of the π-system of monoaryl-substituted norbornadienes with acetylene bridges: influence on the photochemical conversion and storage of light energy

• Robin Schulte,
• Dustin Schade,
• Thomas Paululat,
• Till J. B. Zähringer,
• Christoph Kerzig and
• Heiko Ihmels

Beilstein J. Org. Chem. 2024, 20, 3061–3068, doi:10.3762/bjoc.20.254

• new, energy-intensive technologies and overconsumption of energy [1][2]. In this context, windpower plants and solar photovoltaic systems have become increasingly important contributions to the overall available energy, although both technologies still pose some problems regarding the storage of the

Chemical structure metagenomics of microbial natural products: surveying nonribosomal peptides and beyond

• Thomas Ma and
• John Chu

Beilstein J. Org. Chem. 2024, 20, 3050–3060, doi:10.3762/bjoc.20.253

• of almost any bioactivity of interest that originate from plants, fungi, and even animals (such as sponges and corals). Perspective BGF can access only a fraction of the natural product chemical space For nearly a century, BGF has been the method of choice and identified the vast majority of natural

• . Structure prediction of natural products other than NRPs and PKs has historically progressed slower. However, it was not due to a lack of data. Indeed, terpenoids and alkaloids are the two largest families of natural products in plants and also represent a sizable minority in microorganisms. The lagging

N-Glycosides of indigo, indirubin, and isoindigo: blue, red, and yellow sugars and their cancerostatic activity

• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 2840–2869, doi:10.3762/bjoc.20.240

• anticancer activity of these compounds. Keywords: cancerostatic activity; carbohydrates; heterocycles; N-glycosides; indirubin; Introduction Indigo (1a), known for more than 6000 years and originally produced from indigo plants in India, represents a famous traditional blue pigment which was an expensive

• controlled by such protein kinases. Therefore, the investigation of the influence of drugs on protein kinases plays an important role in current medicinal chemistry. Indigo naturalis is a traditional drug, derived from indigo plants, which has been used in China for centuries and also more recently against

Natural resorcylic lactones derived from alternariol

• Joachim Podlech

Beilstein J. Org. Chem. 2024, 20, 2171–2207, doi:10.3762/bjoc.20.187

• interesting biological activities. Keywords: biosynthesis; fungal metabolites; polyketides; resorcylic lactones; total synthesis; Introduction Alternariol and some of its derivatives are ubiquitous as fungal metabolites present in infested plants and in food and feed, but similarly in soil, in wallpapers

• has been investigated thoroughly on its biological activities, especially on its toxicity [6][12]. Its phytotoxicity has already been noted in the first reports; it induced chlorosis when injected to the leaves of tobacco plants [110]. It turned out to be cytotoxic against HeLa and lymphoma L5178Y

Computational toolbox for the analysis of protein–glycan interactions

• Ferran Nieto-Fabregat,
• Maria Pia Lenza,
• Angela Marseglia,
• Cristina Di Carluccio,
• Antonio Molinaro,
• Alba Silipo and
• Roberta Marchetti

Beilstein J. Org. Chem. 2024, 20, 2084–2107, doi:10.3762/bjoc.20.180

• constituting glycoproteins or glycolipids, respectively. Recently, glycan structures exposed on the cellular membrane have also been found to be associated with tRNA [2]. In other species, such as prokaryotes, plants or fungi, glycoconjugates comprise the cell wall, playing critical metabolic, structural and

• for humans, animals and plants, including drug design [14][15], vaccine development [15][16] and numerous other possibilities in the field of carbohydrate chemistry and biology. Notably, the regulation of the host immune response is often mediated by glycans, particularly through their recognition by

Allostreptopyrroles A–E, β-alkylpyrrole derivatives from an actinomycete Allostreptomyces sp. RD068384

• Marwa Elsbaey,
• Naoya Oku,
• Mohamed S. A. Abdel-Mottaleb and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2024, 20, 1981–1987, doi:10.3762/bjoc.20.174

• S55 in Supporting Information File 1). Biosynthetically, pyrrole-2-carboxylic acid is known to be derived from ʟ-proline [2]. Similarly, pyrrole-2-carbaldehydes have been isolated from various natural sources including plants, marine invertebrates, and fungi [7], while 1–5 are the first to have formyl

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

• approach" merging efficient enzymatic synthesis – traditionally employed in the biosynthesis of natural products by microorganisms and plants – with precise chemical synthesis conducted by chemists. Chemo-enzymatic total syntheses reported recently fall into three main categories based on the purpose for

• ), trichodimerol (2), chalcomoracin (3), tylactone (4), and saframycin A (5), as well as a number of analogues of these natural products (Scheme 1). The overview of all five natural products begins with a description of the well-studied biosynthetic strategies evolved by microorganisms and plants. Biosynthetic

• highly substituted methyl cyclohexene core were isolated from plants of the Moraceae family as phytoalexins (Scheme 5) [44]. Since more than 160 related compounds have been discovered in an optically active form, Masamune, Takahashi, and colleagues postulated that the core scaffold is biosynthesized via

Polymer degrading marine Microbulbifer bacteria: an un(der)utilized source of chemical and biocatalytic novelty

• Weimao Zhong and
• Vinayak Agarwal

Beilstein J. Org. Chem. 2024, 20, 1635–1651, doi:10.3762/bjoc.20.146

• invertebrates and plants, perhaps hinting at these molecules being widely used alphabets in inter-organismal chemical cross talk. Non-ribosomally synthesized peptidic natural products Assembly line non-ribosomal peptide synthetases (NRPSs) are routinely detected to be encoded in Microbulbifer genomes [141]. An

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

• discovering diverse natural products from bacteria and fungi. In plants, this approach is often more limited due to the lack of available annotated genomes and transcriptomes combined with a less consistent clustering of biosynthetic genes. The recently identified burpitide class of ribosomally synthesized

• 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

• transcriptomic data sets, we uncover the potential distribution of split burpitide precursor peptides in Streptophyta. Metabolomic analysis of target plants confirms our bioinformatic predictions of new cyclopeptide alkaloids from both known and new sources. Keywords: burpitides; natural products; plants; RiPPs

Computation-guided scaffold exploration of 2E,6E-1,10-trans/cis-eunicellanes

• Zining Li,
• Sana Jindani,
• Volga Kojasoy,
• Teresa Ortega,
• Erin M. Marshall,
• Khalil A. Abboud,
• Sandra Loesgen,
• Dean J. Tantillo and
• Jeffrey D. Rudolf

Beilstein J. Org. Chem. 2024, 20, 1320–1326, doi:10.3762/bjoc.20.115

• family members in bacteria and plants [4], these diterpenoids have four main structural differences: the number and location of oxidized carbons, the absence or presence of transannular ether bridges, the configuration (cis or trans) of the bicyclic ring fusion, and the presence and configuration (E or Z

Stability trends in carbocation intermediates stemming from germacrene A and hedycaryol

• Naziha Tarannam,
• Prashant Kumar Gupta,
• Shani Zev and
• Dan Thomas Major

Beilstein J. Org. Chem. 2024, 20, 1189–1197, doi:10.3762/bjoc.20.101

• in a terpene hydrocarbon, or through nucleophilic water attack, yielding a terpene alcohol [5]. To date, about 80,000 terpenes and terpenoids have been discovered [3], approx. 10% of which are sesquiterpenes, composed of 15-carbon skeletons [6][7]. Sesquiterpenes are mainly distributed in plants and

• anticancer, antimalarial, antibacterial, and antiviral activity [8][9]. For instance, the well-known artemisinin family of drugs, which is currently the first line of treatment against malaria, is a sesquiterpene lactone [10]. Sesquiterpenes produced by plants [10] also have plant growth regulating and

Enhancing structural diversity of terpenoids by multisubstrate terpene synthases

• Min Li and
• Hui Tao

Beilstein J. Org. Chem. 2024, 20, 959–972, doi:10.3762/bjoc.20.86

• diphosphate substrates MSTSs from plants Substrate-promiscuous TSs are widely spread in plants, which mainly produce linear terpenoids such as linalool (6), (E)-nerolidol (7) and (E,E)-α-farnesene (8) (Figure 2) [14][15]. Most plant MSTSs accept two prenyl substrates: C5 and C10 [16], C10 and C15 [17][18][19

• different subcellular compartments may facilitate the generation of multiple terpenoids in plants. Recently, in addition to linear terpenoid-producing TSs, MSTSs that form cyclic terpenoids have been discovered in plants, further increasing our understanding of chemodiversity and biosynthesis of plant

• terpenoids. LcTPS2 from Leucosceptrum canum was characterized as a versatile TS that generated six macrocyclic sesterterpenoids (11–16) and two macrocyclic diterpenoids (17,18), representing the first macrocyclic terpenoids isolated from plants (Table 1, Figure 2) [19]. In addition to linear prenyl

Activity assays of NnlA homologs suggest the natural product N-nitroglycine is degraded by diverse bacteria

• Kara A. Strickland,
• Brenda Martinez Rodriguez,
• Ashley A. Holland,
• Shelby Wagner,
• Michelle Luna-Alva,
• David E. Graham and
• Jonathan D. Caranto

Beilstein J. Org. Chem. 2024, 20, 830–840, doi:10.3762/bjoc.20.75

• producers and of NNG is unknown. Additionally, NNG’s physiological function is unknown, but it is toxic to plants, mice, and Gram-negative bacteria [25][26]. While there is no direct evidence of the mechanism of this toxicity, NNG has been shown to competitively inhibit succinate dehydrogenase, a component

• , reductively decomposes the nitramine functionality of RDX to form •NO2 [38], a toxic reactive nitrogen species. Additionally, NNG is a structural analog of another natural product 3-nitropropionate (3NP) found in plants and fungi [39]. This highly toxic compound inhibited succinate dehydrogenase and other

Discovery and biosynthesis of bacterial drimane-type sesquiterpenoids from Streptomyces clavuligerus

• Dongxu Zhang,
• Wenyu Du,
• Xingming Pan,
• Xiaoxu Lin,
• Fang-Ru Li,
• Qingling Wang,
• Qian Yang,
• Hui-Min Xu and
• Liao-Bin Dong

Beilstein J. Org. Chem. 2024, 20, 815–822, doi:10.3762/bjoc.20.73

• University, Nanjing 211198, China 10.3762/bjoc.20.73 Abstract Drimane-type sesquiterpenoids (DMTs) are characterized by a distinctive 6/6 bicyclic skeleton comprising the A and B rings. While DMTs are commonly found in fungi and plants, their presence in bacteria has not been reported. Moreover, the

• performs a similar role to DrtB, engaging two P450s (AncE and AncB) to synthesize (+)-isoantrocin and (−)-antrocin [18]. Notably, the P450s identified in fungi and plants predominantly modify the B-ring of DMTs [15][16][18]. DMTs are commonly found in plants and fungi [6][9][13][15]. While enzymes

• derivatives 7–9. This study marks the first discovery of natural DMTs from bacteria and unveils the role of CavA in a novel late-stage modification pathway, expanding DMT biosynthesis beyond fungi and plants. Results and Discussion Discovery of three DMTs in S. clavuligerus S. clavuligerus is notably

Methodology for awakening the potential secondary metabolic capacity in actinomycetes

• Shun Saito and
• Midori A. Arai

Beilstein J. Org. Chem. 2024, 20, 753–766, doi:10.3762/bjoc.20.69

• environment in order to activate silent genes in actinomycetes. Actinomycetes mainly inhabit soils, but they are widely symbiotic with plants [103], insects [104], and other organisms [105][106], and there are reports of their secondary metabolites controlling their own physiological functions or functioning

Research progress on the pharmacological activity, biosynthetic pathways, and biosynthesis of crocins

• Zhongwei Hua,
• Nan Liu and
• Xiaohui Yan

Beilstein J. Org. Chem. 2024, 20, 741–752, doi:10.3762/bjoc.20.68

• -inflammatory properties, hepatorenal protection, and anticancer activity. They are often used as coloring and seasoning agents. Due to the limited content of crocins in plants and the high cost of chemical synthesis, the supply of crocins is insufficient to meet current demand. The biosynthetic pathways for

• , which complicates matching supply to demand. Engineering microbial strains for the heterologous production of rare natural products has emerged as a promising approach [18][19]. With the elucidation of the biosynthetic pathways for crocins in plants, the heterologous production of crocin and crocetin

• roots of plants. The content varies significantly among different plant species and different parts within the same plant. For instance, in C. sativus, crocins are predominantly accumulated in the stigma, but in G. jasminoides, they are primarily stored in the pulp. The traditional methods for

Genome mining of labdane-related diterpenoids: Discovery of the two-enzyme pathway leading to (−)-sandaracopimaradiene in the fungus Arthrinium sacchari

• Fumito Sato,
• Terutaka Sonohara,
• Shunta Fujiki,
• Akihiro Sugawara,
• Yohei Morishita,
• Taro Ozaki and
• Teigo Asai

Beilstein J. Org. Chem. 2024, 20, 714–720, doi:10.3762/bjoc.20.65

• TCs subsequently catalyze the second cyclization to construct the polycyclic scaffold of natural products [5]. In plants, two independent αβγ tri-domain TCs, ent-CPP synthase (CPS) and ent-kaurene synthase (KS), are often used for this conversion [6], and a single bifunctional enzyme that successively

• employed [8]. In fungi, only bifunctional enzymes consisting of αβγ tri-domains have been identified to date [9][10][11][12][13]. In the evolutionary aspects, fungal bifunctional TCs are proposed to have been acquired from plants by a horizontal gene transfer event [14] and eukaryotic tri-domain TCs are

New variochelins from soil-isolated Variovorax sp. H002

• Jabal Rahmat Haedar,
• Aya Yoshimura and
• Toshiyuki Wakimoto

Beilstein J. Org. Chem. 2024, 20, 692–700, doi:10.3762/bjoc.20.63

• other than variochelins, including vacidobactin from V. paradoxus S110, variobactin from V. paradoxus P4B, and imaqobactin from Variovorax sp. RKJM285, suggesting their significant role in interactions with both plants and other microbes in near-surface soil through iron photocycling [5][11][12]. In

Introduction of a human- and keyboard-friendly N-glycan nomenclature

• Friedrich Altmann,
• Johannes Helm,
• Martin Pabst and
• Johannes Stadlmann

Beilstein J. Org. Chem. 2024, 20, 607–620, doi:10.3762/bjoc.20.53

• always the same core. Years later, colleagues from in- and outside my institution engaged in “humanization” of plant N-glycans, which at first entailed removal of the plant-typical residues α1,3-fucose and xylose [32][33]. Later, the glyco-engineering of plants with the introduction of human features

• strictly always in α1,6. If you only work with mammalian samples you may content yourself with this simplification. However, as insect cells and plants are of relevance as biotechnological expression systems for pharmaceutical glycoproteins, we must consider that here fucose may also be found in the α1,3

• plants and some non-vertebrate animals [43][44], the β-mannosyl residues may instead be decorated with a xylose residue, for which the letter X is added after the term for the 3-arm (Figure 4). Fucose on antennae Lewis fucoses introduce branching of the antenna. IUPAC nomenclature uses square brackets to

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

• , and anticancer properties [6][7]. Historically, most alkaloids were isolated from higher plants, with a significant number found in the Apocynaceae family. Notable examples such as vinblastine, vinorelbine, vincristine, and vindesine have gained prominence as effective anticancer drugs [6][7][8][9][10

Synthesis and biological profile of 2,3-dihydro[1,3]thiazolo[4,5-b]pyridines, a novel class of acyl-ACP thioesterase inhibitors

• Jens Frackenpohl,
• David M. Barber,
• Guido Bojack,
• Birgit Bollenbach-Wahl,
• Ralf Braun,
• Rahel Getachew,
• Sabine Hohmann,
• Kwang-Yoon Ko,
• Karoline Kurowski,
• Bernd Laber,
• Rebecca L. Mattison,
• Thomas Müller,
• Anna M. Reingruber,
• Dirk Schmutzler and
• Andrea Svejda

Beilstein J. Org. Chem. 2024, 20, 540–551, doi:10.3762/bjoc.20.46

• with emphasis on the structural diversity of small-molecule ligands. In this context, acyl-acyl carrier protein (acyl-ACP) thioesterase inhibitors have shown a remarkable variability. Fatty acid thioesterase (FAT) enzymes represent a family of proteins exclusively found in higher plants. They mediate

• 2,3-dihydro[1,3]thiazolo[4,5-b]pyridines, i.e., 13a–c, and 7a–c, the acylated analogues 14a–c and 16a–f, as well as selected aminoboranes 17d and 17e, were tested for target affinity in dedicated in vitro tests, as well as for herbicidal effects in vivo upon preemergence application to plants. Based

• on our experience with thiazolopyridine-based FAT inhibitors [12][13], five representative grass weeds (ALOMY, ECHCG, LOLRI, POAAN, and SETVI) were chosen as model plants to assess initial preemergence activity using a dose rate of 320 g/ha, whereas in vitro tests were carried out using FAT A

A new analog of dihydroxybenzoic acid from Saccharopolyspora sp. KR21-0001

• Rattiya Janthanom,
• Yuta Kikuchi,
• Hiroki Kanto,
• Tomoyasu Hirose,
• Arisu Tahara,
• Takahiro Ishii,
• Arinthip Thamchaipenet and
• Yuki Inahashi

Beilstein J. Org. Chem. 2024, 20, 497–503, doi:10.3762/bjoc.20.44

• and fungi at 20 µg per disc in the paper disc diffusion method. Dihydroxybenzoic acid (DHBA) plays a role in anti-inflammatory, antihyperglycemic, antiapoptotic, and antioxidant processes [14]. 2,3-DHBA is found in nature and is produced by various plants (e.g., Gentiana rigerscense and Vinca minor

Green and sustainable approaches for the Friedel–Crafts reaction between aldehydes and indoles

• Periklis X. Kolagkis,
• Eirini M. Galathri and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2024, 20, 379–426, doi:10.3762/bjoc.20.36

• infects a great number of agricultural plants, causing great harm to production by evolving to resist most of the existing drugs. Thus, BIMs have emerged as a new natural alternative class of antiviral agents, surpassing commonly used drugs such as ribavirin that has been observed to damage the DNA

Elucidating the glycan-binding specificity and structure of Cucumis melo agglutinin, a new R-type lectin

• Jon Lundstrøm,
• Emilie Gillon,
• Valérie Chazalet,
• Nicole Kerekes,
• Antonio Di Maio,
• Ten Feizi,
• Yan Liu,
• Annabelle Varrot and
• Daniel Bojar

Beilstein J. Org. Chem. 2024, 20, 306–320, doi:10.3762/bjoc.20.31

• biology, and biomedicine. These carbohydrate-binding proteins boast a range of functions, acting as recognition modules in cell–molecule and cell–cell interactions, thereby playing vital roles in immune defense, regulation of growth, and apoptosis [1]. In plants, they serve as essential components in

• abovementioned applications are R-type lectins, especially those derived from plants. Examples include SNA (from Sambucus nigra, binding Neu5Acα2-6 [14]) or RCA1 (from Ricinus communis, binding terminal β-linked galactose [15]). Yet, despite the extensive studies on plant lectins, particularly R-type lectins

• in which its preferred binding motifs occur (O-glycans, milk glycans, GAGs) are absent from most plants, including melons. We thus hypothesize that the role of this lectin might be to recognize non-self epitopes, such as for protection against pathogens, which is a common function in plant lectins [3

Photochromic derivatives of indigo: historical overview of development, challenges and applications

• Gökhan Kaplan,
• Zeynel Seferoğlu and
• Daria V. Berdnikova

Beilstein J. Org. Chem. 2024, 20, 228–242, doi:10.3762/bjoc.20.23

• (Figure 14). Indirubin (26) is a purple colored dye that can be found in Isatis tinctoria and Indigofera tinctoria plants along with indigo and its derivatives or can be obtained as a metabolism product of some bacteria [68]. Given to the wide range of biological activities, including anticancer and anti