Synthesis of electrophile-tethered preQ₁ analogs for covalent attachment to preQ₁ RNA

• Laurin Flemmich and
• Ronald Micura

Beilstein J. Org. Chem. 2025, 21, 483–489, doi:10.3762/bjoc.21.35

• , Scheme 1A) belong to the 7-deazapurine family, which contain a pyrrolo[2,3-d]pyrimidine core. A rich pool of natural 7-deazapurine products has been identified, often (apparently) sharing a common biosynthetic pathway. Their functions are diverse; while some have been identified as having antifungal or

Antibiofilm and cytotoxic metabolites from the entomopathogenic fungus Samsoniella aurantia

• Rita Toshe,
• Syeda J. Khalid,
• Blondelle Matio Kemkuignou,
• Esteban Charria-Girón,
• Paul Eckhardt,
• Birthe Sandargo,
• Kunlapat Nuchthien,
• J. Jennifer Luangsa-ard,
• Till Opatz,
• Hedda Schrey,
• Sherif S. Ebada and
• Marc Stadler

Beilstein J. Org. Chem. 2025, 21, 327–339, doi:10.3762/bjoc.21.23

• (PKS–NRPS) [13]. Based on the structural relations between farinosones and tenellins differing only in the side chain length/the number of conjugated double bonds, farinosones were also postulated to be synthesized adopting a similar biosynthetic pathway. The biosynthesis of farinosones (Figure 4

• experimental (black) and simulated Boltzmann-averaged (red: (2’S,3’S,12S)-1; green: (2’S,3’S,12R)-1) ECD spectra of compound 1. A plausible biosynthetic pathway of 1–3. Biofilm inhibition and eradication assessment via CV staining assay. A) S. aureus biofilm inhibition by farinosone D (1) and farinosone A (2

The scent gland composition of the Mangshan pit viper, Protobothrops mangshanensis

• Jonas Holste,
• Paul Weldon,
• Donald Boyer and
• Stefan Schulz

Beilstein J. Org. Chem. 2024, 20, 2644–2654, doi:10.3762/bjoc.20.222

• formation requires a finely tuned biosynthetic machinery that deviates from the common fatty acid biosynthetic pathway operating, also in snakes, that we discussed earlier [8]. Fatty acids in SGS have been proposed to act as insecticides against ants or other harmful arthropods as they are thought to be

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

• hybrid syntheses of cotylenol (1) and brassicicenes [19]. The key oxidative allylic rearrangement was conducted enzymatically, while the skeletal rearrangement originally mediated by P450 enzymes in the biosynthetic pathway was achieved through chemical transformation. Hence, this strategy can be

• biosynthetic pathway as proposed by Cox, based on bioinformatic analyses of polyketide synthase (PKS) modules and in vitro studies. Initially, highly reducing iterative polyketide synthase (HR-iPKS) SorbA forms the thioester 30 on its acyl carrier protein (ACP) domain from acetate and two units of malonyl-CoA

• isolated [47][49]. As shown in Scheme 5A, the proposed biosynthetic pathway of chalcomoracin (3) commence with the addition of three C2 units from the acetate pathway to 4-coumaroyl-CoA supplied from the shikimate pathway, leading to compound 42 [47]. Subsequent Claisen condensation, dehydration and

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

• a sponge-derived Microbulbifer strain [73]. This deep purple pigment has been isolated from several other bacterial genera [129], including but not limited to the epiphytic commensal marine bacteria of the genus Pseudoalteromonas where the biosynthetic pathway was eventually established [130][131

Cofactor-independent C–C bond cleavage reactions catalyzed by the AlpJ family of oxygenases in atypical angucycline biosynthesis

• Jinmin Gao,
• Liyuan Li,
• Shijie Shen,
• Guomin Ai,
• Bin Wang,
• Fang Guo,
• Tongjian Yang,
• Hui Han,
• Zhengren Xu,
• Guohui Pan and
• Keqiang Fan

Beilstein J. Org. Chem. 2024, 20, 1198–1206, doi:10.3762/bjoc.20.102

• conditions [25]. This observation not only affirmed 8 as an intermediate in jadomycin biosynthesis but also suggested a role as a more electron-rich substrate with the potential for direct activation of molecular oxygen. We first confirmed the generation of 8 in the biosynthetic pathway of kinamycin. The

• as direct substrates for AlpJ-family oxygenases. However, the dominant biosynthetic pathway in vivo remains unclear. Given that 8 has been experimentally validated as the authentic product of the JadH/AlpG-catalyzed reaction, it is recognized as a bona fide intermediate in angucycline biosynthesis

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

• been utilized. New building blocks with irregular carbon numbers broaden the diversity of terpenoid structures. However, more systematic studies on noncanonical terpenoids are needed to study their biological activities. Biosynthetic pathway of terpenoids. Valuable terpenoids, noncanonical C11 and C16

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

• a precursor for derivatives 2–4. The biosynthetic pathway is likely to involve enzymatic modifications at the C-2 and C-3 positions, leading to the formation of diols 2 and 3, with additional oxidation steps producing ketone 4 (Figure 3b). This supports the presence of three P450s in the cav cluster

• identified the cav BGC responsible for the production of compounds 2 and 3 and elucidated its biosynthetic pathway by heterologous expression. Specifically, our study unveils a P450, CavA, capable of oxidizing the C-2 and C-3 positions of drimenol, representing the first native P450 that activates the A-ring

• . (b) HPLC chromatograms comparing standards with metabolites extracted from S. clavuligerus cultured in YMS and XTM media. Biosynthesis of drimenol congeners. (a) The cav BGC. (b) Proposed biosynthetic pathway for drimenol congeners 2–4. (c) HPLC analysis of metabolites from genetically engineered

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

• , aiming to lay the foundation for the large-scale production of these valuable natural products by using engineered microbial cell factories. Keywords: biosynthetic pathway; crocetin; crocins; metabolic engineering; pharmacological activity; Introduction Crocins are hydrophilic apocarotenoids mainly

Chemoenzymatic synthesis of macrocyclic peptides and polyketides via thioesterase-catalyzed macrocyclization

• Senze Qiao,
• Zhongyu Cheng and
• Fuzhuo Li

Beilstein J. Org. Chem. 2024, 20, 721–733, doi:10.3762/bjoc.20.66

• at the biomimetic position (17a), which not only alleviated the epimerization in the macrolactamization process compared to other positions, but also enabled investigation of its biosynthetic pathway [60]. They also identified a stand-alone enzyme known as SurE, which is classified as a penicillin

• 2005, Sherman and co-workers reported a chemoenzymatic approach through the stereospecific macrocyclization based on the identification of the thioesterase domain (CrpTE) from the cryptophycin biosynthetic pathway, which demonstrated that the CrpTE has both high efficiency in generating the 16-membered

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

• variochelin biosynthetic gene cluster. Biosynthetic pathway of variochelins Nett et al. reported the variochelin biosynthetic gene cluster (NCBI accession number KT900023) encoded in V. boronicumulans, although it has not yet been experimentally validated. In the draft genome sequence of Variovorax sp. H002

• (Figure 3b). As a result, the varG knock-out mutant no longer produced 1–5, validating that the var biosynthetic gene cluster is indispensable for variochelin production in Variovorax sp. H002 (Figure 3b). As 1–5 share a common biosynthetic pathway, the Hya and the 4-amino-7-guanidino-3-hydroxy-2

• by diamonds. EIMS of DMOX derivatized free fatty acids derived from variochelins C–E (3–5). (a) 3, (b) 4, and (c) 5. (a) Plausible biosynthetic pathway of variochelin A–E (1–5). The circles represent domains: A: adenylation domain, C: condensation domain, PCP: peptide carrier protein, E

Production of non-natural 5-methylorsellinate-derived meroterpenoids in Aspergillus oryzae

• Jia Tang,
• Yixiang Zhang and
• Yudai Matsuda

Beilstein J. Org. Chem. 2024, 20, 638–644, doi:10.3762/bjoc.20.56

• biosynthetic pathway and those from DMOA-derived meroterpenoid pathways, successfully yielding six unnatural 5-MOA-derived meroterpenoid species. Results and Discussion To synthesize unnatural meroterpenoid molecules, we sought to generate a series of 5-MOA-derived meroterpenoids by utilizing the terpene

• the structures of 1 and 2 were deduced based on their HRMS spectra and the predicted biosynthetic pathway. Biosynthetic mechanisms of the 5-MOA-derived meroterpenoids obtained in this study. In the reaction by InsA7, the cyclization should proceed via a pre-boat-chair conformation, and the

• structures, the biosynthetic pathway, and NMR data and spectra. Acknowledgements We thank Prof. Katsuya Gomi (Tohoku University), Prof. Katsuhiko Kitamoto (University of Tokyo), and Prof. Jun-ichi Maruyama (University of Tokyo) for providing the expression vectors and fungal strain. We are grateful to Dr

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

• pentasaccharide. No further definitions are required as the residues preceding the GlcNAcs are unambiguously determined by the biosynthetic pathway of N-glycans. Action of hexosaminidases would generate two isomers with just one GlcNAc and a terminal mannose residue. By defining the reading direction, we can

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

• methyltransferase near BGC 7.3, suggesting its involvement in adding a methoxy group at the C16 position of compound 1. From these key enzyme genes, we propose a hypothetical biosynthetic pathway (Figure 5). Compounds 1 and 2 are hypothesized to be synthesized from a tryptophan precursor via a shared biosynthetic

• 1 and those previously reported. This suggests that the formation of the quinoline ring in compound 1 may represent a new and unreported biosynthetic pathway. Moreover, to address the low yields that hindered the determination of absolute stereochemistry, we attempted to boost the production of

• pathway (Figure 5). Briefly, the prenyl group is attached to tryptophan through a prenylation reaction catalyzed by ShnA, followed by the decarboxylation of the carboxy group by ShnC. Subsequently, compound 2 is formed by the addition of succinimide to N15 in 1 via a reaction catalyzed by ShnB. The

A myo-inositol dehydrogenase involved in aminocyclitol biosynthesis of hygromycin A

• Michael O. Akintubosun and
• Melanie A. Higgins

Beilstein J. Org. Chem. 2024, 20, 589–596, doi:10.3762/bjoc.20.51

• dehydrogenase Hyg17 to form neo-inosose, followed by a transamination to neo-inosamine-2 by the aminotransferase Hyg8. The methyltransferase Hyg6 would then install a methyl group which would set up cyclization of the methylenedioxy group by Hyg7. This biosynthetic pathway has been proposed based on gene

• bodies when recombinantly produced by various E. coli expression strains. However, we were able to obtain pure soluble protein when expressing Hyg17 in a Rhodococcus expression system (Supporting Information File 1, Figure S1) [10][11]. According to the proposed hygromycin A biosynthetic pathway, Hyg17

• completed using the enzyme function initiative (EFI-GNT) web tool [31][32]. Gene clusters were compared using CAGECAT [33]. SSNs and GNNs were visualized using Cystoscape [34]. Proposed biosynthetic pathway for the aminocyclitol from hygromycin A. Hyg17 activity. Reactions with Hyg17 and (a) various

Recent developments in the engineered biosynthesis of fungal meroterpenoids

• Zhiyang Quan and
• Takayoshi Awakawa

Beilstein J. Org. Chem. 2024, 20, 578–588, doi:10.3762/bjoc.20.50

• will be discussed as examples of engineering biosynthetic pathways and key enzymes involved in fungal meroterpenoid biosynthesis. Furthermore, a construction of the artificial biosynthetic pathway composed of the fungal meroterpenoids pathway and the pathway from other species, in fungal host

• produce daurichromenic acid (61) (Figure 9), a plant-derived meroterpenoid that exhibits anti-HIV activity [40]. Furthermore, by expressing AscD, a fungal halogenase from the ascochlorin biosynthetic pathway, the authors succeeded in biosynthesizing 62, an unnatural meroterpneoid, chloro-daurichromenic

Pseudallenes A and B, new sulfur-containing ovalicin sesquiterpenoid derivatives with antimicrobial activity from the deep-sea cold seep sediment-derived fungus Pseudallescheria boydii CS-793

• Zhen Ying,
• Xiao-Ming Li,
• Sui-Qun Yang,
• Hong-Lei Li,
• Xin Li,
• Bin-Gui Wang and
• Ling-Hong Meng

Beilstein J. Org. Chem. 2024, 20, 470–478, doi:10.3762/bjoc.20.42

• data for compound 3 was conducted (Table 1) and its absolute configurations were assigned as 1R, 2S, 6R, 7R, 8S by single-crystal X-ray diffraction analysis with a Flack parameter of 0.024(6) (Figure 4). A plausible biosynthetic pathway for compounds 1–5 is proposed as shown in Scheme 1. In this

• . Key 1H-1H COSY (bond lines), and HMBC (red arrows) correlations of 1–3. NOE correlations of compounds 1 and 2 (solid line indicates β-orientation and dashed lines represent α-orientation). X-ray crystal structure of compounds 1–3 (with a thermal ellipsoid probability of 50%). Proposed biosynthetic

• pathway for compounds 1–5. 1H (500 MHz) and 13C NMR (125 MHz) data for compounds 1–3. Antimicrobial activities of compounds 1–3 (MIC).a Supporting Information Supporting Information File 5: Selected 1D and 2D NMR, and HRESIMS spectra of compounds 1 and 2, and 1D NMR spectra of compounds 3–5. Supporting

Development of a chemical scaffold for inhibiting nonribosomal peptide synthetases in live bacterial cells

• Fumihiro Ishikawa,
• Sho Konno,
• Hideaki Kakeya and
• Genzoh Tanabe

Beilstein J. Org. Chem. 2024, 20, 445–451, doi:10.3762/bjoc.20.39

• modular synthases [5]. They used the inhibitors of individual domains to investigate the biosynthetic pathway of blue pigment synthetase A, which produces the blue pigment indigoidine, and demonstrated that their results complement the proposed biosynthetic pathway. Furthermore, among the catalytic domain

Identification of the p-coumaric acid biosynthetic gene cluster in Kutzneria albida: insights into the diazotization-dependent deamination pathway

• Seiji Kawai,
• Akito Yamada,
• Yohei Katsuyama and
• Yasuo Ohnishi

Beilstein J. Org. Chem. 2024, 20, 1–11, doi:10.3762/bjoc.20.1

• , Bunkyo-ku, Tokyo 113-8657, Japan 10.3762/bjoc.20.1 Abstract Recently, we identified the biosynthetic gene cluster of avenalumic acid (ava cluster) and revealed its entire biosynthetic pathway, resulting in the discovery of a diazotization-dependent deamination pathway. Genome database analysis revealed

• vigorously used to search for novel compounds in recent years due to the rapid improvement of DNA sequence technologies and computational approaches to analyze BGCs [1][3]. Our research group previously identified the secondary metabolite-specific nitrous acid biosynthetic pathway, named ANS (aspartate

• biosynthetic pathway [13]. In this pathway, 3-amino-4-hydroxybenzoic acid (3,4-AHBA, 1), synthesized by AvaH and AvaI, is loaded onto AvaA3 (carrier protein) by AvaA1 (AMP-dependent ligase), resulting in 3,4-AHBA-AvaA3. A highly reducing type II polyketide synthase (PKS) system [15][16] (AvaA2, A4, A5, and A8

Unraveling the role of prenyl side-chain interactions in stabilizing the secondary carbocation in the biosynthesis of variexenol B

• Moe Nakano,
• Rintaro Gemma and
• Hajime Sato

Beilstein J. Org. Chem. 2023, 19, 1503–1510, doi:10.3762/bjoc.19.107

• biosynthesis of trichobrasilenol [22], by combined methods of computational and experimental chemistry. Recently, Dickschat et al. reported the synthesis of a novel diterpene compound, variexenol B, using a substrate analogue called iso-GGPP (Scheme 1) [23]. This biosynthetic pathway has two interesting

• hyperconjugation determines whether the reaction proceeds in a stepwise or concerted manner. The second interesting aspect of the biosynthesis of variexenol B is that the biosynthetic pathway involves an intermediate with an exomethylene group. A terpene with an exomethylene group as a starting material is rare

• carbocation and the prenyl side chain. Figure 1 shows the computed biosynthetic pathway and energy diagram without cation–π interaction, while Figure 2 shows the computed biosynthetic pathway including cation–π interaction from the prenyl side chain. Our research started with the application of DFT

Functions of enzyme domains in 2-methylisoborneol biosynthesis and enzymatic synthesis of non-natural analogs

• Binbin Gu,
• Lin-Fu Liang and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2023, 19, 1452–1459, doi:10.3762/bjoc.19.104

• for sodorifen [38] – potentially allow for an evolution towards a natural biosynthetic pathway for C12 monoterpenoids. Experimental General synthetic methods Chemicals were purchased from Sigma-Aldrich Chemie GmbH (Steinheim, Germany), Carbolution Chemicals GmbH (St. Ingbert, Germany), or Carl Roth

Cassane diterpenoids with α-glucosidase inhibitory activity from the fruits of Pterolobium macropterum

• Sarot Cheenpracha,
• Ratchanaporn Chokchaisiri,
• Lucksagoon Ganranoo,
• Sareeya Bureekaew,
• Thunwadee Limtharakul and
• Surat Laphookhieo

Beilstein J. Org. Chem. 2023, 19, 658–665, doi:10.3762/bjoc.19.47

• , MeOH); lit. −44 (c 0.05, MeOH)) [18], confirming the same absolute configuration these compounds should be derived from the same biosynthetic pathway. In addition, the ECD spectra of (5S,8R,9S,10R,14S)-1 and its enantiomer were calculated at the B3LYP functional using a TD–DFT method [19]. As

• = 2.7 Hz) and H-6′ (J = 2.7 Hz). The syn orientations of H-15, H-15′, H-16′ and H3-17′ were established from the NOESY correlations of H-15′ to H3-17′, H-16′ and of H-15 to H-16′. From above information, the relative configuration of C-12′ was assigned and supported by the biosynthetic pathway based on

Combretastatins D series and analogues: from isolation, synthetic challenges and biological activities

• Jorge de Lima Neto and
• Paulo Henrique Menezes

Beilstein J. Org. Chem. 2023, 19, 399–427, doi:10.3762/bjoc.19.31

• compounds available in the literature, there is none which focuses only on combretastatins D and their isomers. Therefore, this review is divided into three main parts: the first comprises the isolation of these compounds from natural sources. In the following part, the biosynthetic pathway and the total

• elucidate the chemical structures of the isolated compounds [19]. 2 Synthesis 2.1 Biosynthetic pathway In the literature, there are two possible biosynthetic pathways for the formation of these compounds. The first one was proposed by Pettit and co-workers [16][17] based on tyrosine as the starting material

• ]. IC50 of compounds against α-glucosidase [19]. Biosynthetic pathway proposed by Pettit and co-workers. Biosynthetic pathway towards corniculatolides or isocorniculatolides proposed by Ponnapalli and co-workers. Retrosynthetic approaches. Attempt of total synthesis of 2 by Boger and co-workers employing

Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series

• Cécile Alleman,
• Charlène Gadais,
• Laurent Legentil and
• François-Hugues Porée

Beilstein J. Org. Chem. 2023, 19, 245–281, doi:10.3762/bjoc.19.23

Identification and determination of the absolute configuration of amorph-4-en-10β-ol, a cadinol-type sesquiterpene from the scent glands of the African reed frog Hyperolius cinnamomeoventris

• Angelique Ladwig,
• Markus Kroll and
• Stefan Schulz

Beilstein J. Org. Chem. 2023, 19, 167–175, doi:10.3762/bjoc.19.16

• scent gland macrolides can be biosynthesized by the frogs [7], although the macrolides are produced from the fatty acid biosynthetic pathway. The gas chromatographic separation obtained with the chiral phase also allowed the determination of the identity of the minor diastereomers formed during the