Synthesis of 1,4-azaphosphinine nucleosides and evaluation as inhibitors of human cytidine deaminase and APOBEC3A

• Maksim V. Kvach,
• Stefan Harjes,
• Harikrishnan M. Kurup,
• Geoffrey B. Jameson,
• Elena Harjes and
• Vyacheslav V. Filichev

Beilstein J. Org. Chem. 2024, 20, 1088–1098, doi:10.3762/bjoc.20.96

• bacteria and fungi but not in mammalian cells, acts only on cytosine. Cytidine deaminase (CDA) as a key enzyme in the pyrimidine salvage pathway in mammals deaminates both cytidine and 2'-deoxycytidine. Members of the apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC) family, such as

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

• generate different diterpene skeletons 22–28, which were further converted to diterpenoids by a P450 monooxygenase (CYP99A17) (Table 1, Figure 2) [20]. These findings will enable further investigation of the functions of terpenoids in plants and crops. MSTSs from fungi Fungi are also prolific producers of

• the supply of prenyl substrates can significantly change the product profile of promiscuous TSs, thereby generating terpenes with novel structures. MSTSs from bacteria According to previous studies, plants and fungi are the major producers of terpenoids [30][31][32][33]. Recently, an increasing number

• ) 11–18 products of LcTPS from Leucosceptrum canum; c) 22–28 are products of SiTPS from Setaria italicais using substrates 19–21. The structure of representative terpene products of MSTSs. a) From fungi: compounds 30–33 are produced by the fungal TS FgMS, 34 is the product of wild-type EvVS, and 33 is

Confirmation of the stereochemistry of spiroviolene

• Yao Kong,
• Yuanning Liu,
• Kaibiao Wang,
• Tao Wang,
• Chen Wang,
• Ben Ai,
• Hongli Jia,
• Guohui Pan,
• Min Yin and
• Zhengren Xu

Beilstein J. Org. Chem. 2024, 20, 852–858, doi:10.3762/bjoc.20.77

• cyclization process of fungi-derived deoxyconidiogenol and bacteria-derived spiroviolene by sharing the common C6-cation intermediate IM-3 with cyclopiane skeleton (Scheme 1A). Conclusion We have unambiguously confirmed the structural revision of spiroviolene with cis-oriented 19- and 20-methyl groups by

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

• , the physiological function of its substrate NNG. This compound is one of the few known nitramine natural products and the only one produced by bacteria instead of fungi [22]. Its only known natural sources are strains of Streptomyces bacteria [23][24]. The abundance and distribution of these NNG

• , 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

• biosynthetic pathways for DMTs have been primarily elucidated in fungi, with identified P450s only acting on the B ring. In this study, we isolated and characterized three bacterial DMTs, namely 3β-hydroxydrimenol (2), 2α-hydroxydrimenol (3), and 3-ketodrimenol (4), from Streptomyces clavuligerus. Through

• 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

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

• Fumito Sato Terutaka Sonohara Shunta Fujiki Akihiro Sugawara Yohei Morishita Taro Ozaki Teigo Asai Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan 10.3762/bjoc.20.65 Abstract Labdane-related diterpenoids (LRDs) in fungi are a pharmaceutically important, but

• of TCs in fungi. Keywords: diterpenoids; fungi; genome mining; labdane; terpene cyclase; Introduction Terpenoids are a structurally diverse family of natural products, including more than 80,000 compounds [1]. In the biosynthesis of terpenoids, terpene cyclases (TCs) add structural diversity and

• 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

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

• secondary metabolites, filamentous fungi stand out as the most prolific producers of meroterpenoids [1][2][3]. Representative fungal meroterpenoids of medicinal importance include pyripyropene A, a cholesterol acyltransferase inhibitor [4]; fumagillin, an antimicrobial agent [5]; and mycophenolic acid, a

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

• enzymatic ring-expansion process in their respective fungi. Both shentonins A (1) and B (2) also feature a reduction of a carbonyl to a hydroxy group within the succinimide ring. All isolated compounds were subjected to antimicrobial evaluations, and compound 12 was found to have moderate inhibitory

• ]. Recent studies have revealed that certain fungi are also prolific sources of indole alkaloids, which are among the largest classes of nitrogen-containing secondary metabolites. Characterized by at least one indole moiety and derived from tryptophan or tryptamine, indole alkaloids are known for their

• −1; for 1H NMR (CDCl3, 600 MHz) and 13C NMR (CDCl3, 125 MHz) spectral data, see Table 1; LC–MS (m/z): [M − H]− calcd for 283.2; found, 283.2. Antimicrobial activity evaluation All isolated compounds were dissolved in 1% DMSO and introduced to pathogenic bacteria or fungi in LB or PDB media. The 96

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

• ) were expressed in A. oryzae to produce the intermediate 15. Next, genes encoding a short-chain oxidoreductase (SDR), methyltransferase (MT), cytochrome P450 oxygenase (P450), and FMO from various fungi were additionally expressed in A. oryzae expessing subABCDE to produce 22 bioactive meroterpenoids

• enzyme that oxidizes C-5, thereby reacting with the electron between C-1 and C-2 [38]. In the future, such mutagenesis strategies will be applied to a wider range of oxidases to alter their reactivities and create an expanded range of products. Construction of artificial fungi–plant hybrid biosynthetic

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

• the presence of a new compound designated KR21-0001A (1). The structure was elucidated by NMR, and the absolute stereochemistry was determined by advanced Marfey’s method. The results indicated that 1 is a new analog of dihydroxybenzoic acid. 1 has no antimicrobial activity against bacteria and fungi

• 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

• ), fungi (e.g., Aspergillus sojae and Penicillium roquefortii), and bacteria (e.g., Acinetobacter calcoaceticus, Brucella abortus, and Bacillus sp.) [15]. It is also known to be a component of some natural products, such as enterobactin, showing strong radical scavenging activity or antioxidant activity

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

• alkaloids containing an unprecedented spiro[bicyclo[2.2.2]octane-diketopiperazine] skeleton, chevalinulins A and B, and the first cytochalasin homodimer containing a thioether bridge, verruculoid A, were identified from deep-sea cold seeps-derived fungi and were described to have potent proangiogenic and

• antimicrobial activities [3][4]. As part of our continuing search for bioactive metabolites from deep-sea-derived fungi [3][4][5][6], the fungal strain Pseudallescheria boydii CS-793, which was obtained from sediments collected at the deep-sea cold seep area in the Northeast of the South China Sea, attracted

• –3 were tested against seven human- and marine-derived aquatic pathogenetic bacteria (Edwardsiella tarda, Escherichia coli, Micrococcus luteus, Pseudomonas aeruginosa, Vibrio anguillarum, Vibrio harveyi, and Vibrio vulnificus), and six plant pathogenic fungi (Alternaria brassicae, Colletotrichum

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

• strands of TMV, inhibiting their ability to multiply and cause damage to the plant. At the same time, they also display fungicidal activities against more than fourteen types of common fungi, such as Phytophthora alternaria, based on their DNA damaging properties with the thiourea derivative, showing the

Facile approach to N,O,S-heteropentacycles via condensation of sterically crowded 3H-phenoxazin-3-one with ortho-substituted anilines

• Eugeny Ivakhnenko,
• Vasily Malay,
• Pavel Knyazev,
• Nikita Merezhko,
• Nadezhda Makarova,
• Oleg Demidov,
• Gennady Borodkin,
• Andrey Starikov and
• Vladimir Minkin

Beilstein J. Org. Chem. 2024, 20, 336–345, doi:10.3762/bjoc.20.34

• and its derivatives are widely distributed in nature in microorganisms and fungi, and they represent the key structural units of many important drugs with antibacterial, antifungal, anticancer, anti-inflammatory, and antiviral activities [1][2]. Due to the presence of several reactive centers in the

Secondary metabolites of Diaporthe cameroonensis, isolated from the Cameroonian medicinal plant Trema guineensis

• Bel Youssouf G. Mountessou,
• Élodie Gisèle M. Anoumedem,
• Blondelle M. Kemkuignou,
• Yasmina Marin-Felix,
• Frank Surup,
• Marc Stadler and
• Simeon F. Kouam

Beilstein J. Org. Chem. 2023, 19, 1555–1561, doi:10.3762/bjoc.19.112

• Abstract From a fresh root of Trema guineensis (Ulmaceae), endophytic fungi were isolated, among which a taxon belonging to the new species Diaporthe cameroonensis. This strain was fermented in shake flask batch cultures and the broth was extracted with ethyl acetate. From the crude extract, a hemiketal

• ; endophytic fungi; hemiketal polyketide; Introduction Endophytic fungi are organisms that reside almost ubiquitously inside the fresh healthy tissue of plants, and they may increase the resistance of the host tropical trees to survive in extreme conditions [1]. As the global diversity of endophytic fungi is

• far from being accessed [2][3], they have been considered as an untapped microbial reservoir capable of producing a wide range of structurally unique natural products with potent pharmacological effects [4]. However, the production of biologically active compounds by filamentous fungi, especially

Synthesis and biological evaluation of Argemone mexicana-inspired antimicrobials

• Jessica Villegas,
• Bryce C. Ball,
• Katelyn M. Shouse,
• Caleb W. VanArragon,
• Ashley N. Wasserman,
• Hannah E. Bhakta,
• Allen G. Oliver,
• Danielle A. Orozco-Nunnelly and
• Jeffrey M. Pruet

Beilstein J. Org. Chem. 2023, 19, 1511–1524, doi:10.3762/bjoc.19.108

• (five Gram-positive and four Gram-negative bacteria, and three fungi). Additionally, the crystal structures of two berberine variants are described. Several berberine variants show enhanced antibacterial activity compared to the unaltered plant-derived molecule. We also report promising preliminary

• concern, antimicrobial-resistant microbes are also a threat to the health of the individuals on the international space station (ISS). According to recent studies, a diverse population of bacteria and fungi, including several opportunistic pathogens, have colonized the ISS [5], and many of these strains

• cereus, Bacillus subtilis, Staphylococcus epidermidis, Corynebacterium pseudodiphtheriticum), four Gram-negative bacteria (Escherichia coli, Proteus mirabilis, Enterobacter aerogenes, Enterobacter cloacae), and three fungi (Saccharomyces cerevisiae, Candida albicans, Penicillium chrysogenum). The goal of

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

• bacterial lineages including actinobacteria [4][5][6][7][8][9], myxobacteria [10] and aquatic cyanobacteria [11][12], as well as in liverwort [13] and ascomycete fungi [14]. The odour qualities of 1 may be concentration dependent and range from musty at low concentrations (<1 μg L−1) to camphoraceous at

Two new lanostanoid glycosides isolated from a Kenyan polypore Fomitopsis carnea

• Winnie Chemutai Sum,
• Sherif S. Ebada,
• Didsanutda Gonkhom,
• Cony Decock,
• Rémy Bertrand Teponno,
• Josphat Clement Matasyoh and
• Marc Stadler

Beilstein J. Org. Chem. 2023, 19, 1161–1169, doi:10.3762/bjoc.19.84

• configuration at C-3', it was assigned as S by careful comparison of the 1H and 13C NMR data of compound 1 with those of related lanostane derivatives comprising the 3-hydroxy-3-methylglutaryl moiety produced by some fungi including Fomitopsis pinicola [23], Piptoporus betulinus [13], and Pholiota populnea [35

• , compound 2 was identified as 2α-hydroxy,3α-[(3′S)-4′-carboxyl-3′-hydroxy-3′-methylbutanoyloxy]lanosta-8,24(31)-dien-21-oic acid 21-O-β-ᴅ-glucopyranoside that was named as forpinioside C. Biological activities Compounds 1–4 were tested for their antimicrobial effects against fungi and bacteria; where

• 128: HRESIMS profiles and NMR spectroscopic data of 1, 2 and 4 in CD3OD, and of 3 in (CD3)2S=O; half inhibitory concentrations (IC50) for various mammalian cell lines as well as minimum inhibitory concentrations (MIC) of 1–4 for bacteria, yeasts and filamentous fungi. Acknowledgements The technical

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

• ) against the bacteria Staphylococcus aureus, Bacillus subtilis, Micrococcus luteus, Escherichia coli, Klebsiella pneumoniae, and the fungi Aspergillus niger, Aspergillus terreus, and Aspergillus flavus. Unfortunately, all compounds were found to be inactive [14]. The use of compounds capable to delay

Nostochopcerol, a new antibacterial monoacylglycerol from the edible cyanobacterium Nostochopsis lobatus

• Naoya Oku,
• Saki Hayashi,
• Yuji Yamaguchi,
• Hiroyuki Takenaka and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2023, 19, 133–138, doi:10.3762/bjoc.19.13

• -hexane. The resulting three layers were tested against four Gram-positive bacteria, five Gram-negative bacteria, six fungi, and two yeasts, which detected antibacterial activity against two Gram-positive bacteria, Bacillus subtilis and Staphylococcus aureus, from the 90% aqueous MeOH layer. The

Combining the best of both worlds: radical-based divergent total synthesis

• Kyriaki Gennaiou,
• Antonios Kelesidis,
• Maria Kourgiantaki and
• Alexandros L. Zografos

Beilstein J. Org. Chem. 2023, 19, 1–26, doi:10.3762/bjoc.19.1

• total synthesis of (−)-FR901483 (160) through an aldol reaction, and an intramolecular condensation resulted in the synthesis of (+)-TAN1251C (162, Scheme 13). Divergent synthesis of bipolamine alkaloids (Maimone 2022) [88]: Bipolamines were isolated from the fungi Curvularia sp. IFB Z10 and Bipolaris

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

• sequence-independent manner via analysis of operon-like structures (e.g., promoters or transcription start sites) as shown in fungi by the tool CASSIS/SMIPS [60]. This concept contrasts the commonly used principles that rely on the direct detection of genes via (p)HMMs- or ML-based approaches, both of

Using UHPLC–MS profiling for the discovery of new sponge-derived metabolites and anthelmintic screening of the NatureBank bromotyrosine library

• Sasha Hayes,
• Aya C. Taki,
• Kah Yean Lum,
• Joseph J. Byrne,
• Merrick G. Ekins,
• Robin B. Gasser and
• Rohan A. Davis

Beilstein J. Org. Chem. 2022, 18, 1544–1552, doi:10.3762/bjoc.18.164

• natural product chemists have shifted their attention to marine-derived microorganisms such as bacteria and fungi over the past 10 years [2], sponges continue to be a source of novel and biologically active metabolites and remain an important taxonomic phylum for the discovery of new and bioactive natural

A facile approach to spiro[dihydrofuran-2,3'-oxindoles] via formal [4 + 1] annulation reaction of fused 1H-pyrrole-2,3-diones with diazooxindoles

• Pavel A. Topanov,
• Anna A. Maslivets,
• Maksim V. Dmitriev,
• Irina V. Mashevskaya,
• Yurii V. Shklyaev and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2022, 18, 1532–1538, doi:10.3762/bjoc.18.162

• constructing spirooxindole systems by employing different approaches [6][7][8][9][10][11][12]. Cyclopiazonic acid derivatives such as aspergillins A–E [13] (Figure 1) and speradines C and F [14][15] are secondary metabolites of fungi, and include a furan fragment spiro-fused with 2-oxindole. Cyclopiamides I

Cyclometalated iridium complexes-catalyzed acceptorless dehydrogenative coupling reaction: construction of quinoline derivatives and evaluation of their antimicrobial activities

• Hongling Shui,
• Yuhong Zhong,
• Renshi Luo,
• Zhanyi Zhang,
• Jiuzhong Huang,
• Ping Yang and
• Nianhua Luo

Beilstein J. Org. Chem. 2022, 18, 1507–1517, doi:10.3762/bjoc.18.159

• -triazoquinoline derivatives, and the biological activity evaluation showed that most of the compounds had a higher antibacterial activity (the optimal MIC value was 6.25 mg/mL) against Gram-positive bacteria, Gram-negative bacteria and all tested fungi than the standard ciprofloxacin (Figure 1a). Bodke's group

• compounds was evaluated against Staphylococcus aureus (Gram-positive), Escherichia coli (Gram-negative), and Candida albicans (fungi) mainly by examining the minimum inhibitory concentration (MIC) (Table 4). As shown in Table 4, the compounds 3ab, 3ah, and 3ad showed high antibacterial activities against

Characterization of a new fusicoccane-type diterpene synthase and an associated P450 enzyme

• Jia-Hua Huang,
• Jian-Ming Lv,
• Liang-Yan Xiao,
• Qian Xu,
• Fu-Long Lin,
• Gao-Qian Wang,
• Guo-Dong Chen,
• Sheng-Ying Qin,
• Dan Hu and
• Hao Gao

Beilstein J. Org. Chem. 2022, 18, 1396–1402, doi:10.3762/bjoc.18.144

• their abundant structural architectures [1]. Fusicoccane (FC)-type terpenoids are a subgroup of diterpenoids possessing a unique 5-8-5 tricyclic skeleton, which can be produced by plants, fungi and bacteria [2]. This type of diterpenoids, represented by fusicoccin A and cotylenin A, can serve as

• nature. To date, only five distinct FC-type DTSs, including fungi-derived PaFS/SdnA/MgMS and bacteria-derived CotB2/CpCS, have been reported (Figure 1) [20][21][22][23][24], implying that there still exists a large enzymatic space remaining to be explored. Herein, we characterize a two-gene cluster from

• analyze the function of TadA, we introduced tadA into the quadruple auxotrophic host Aspergillus oryzae NSAR1 (niaD−, sC−, ∆argB, adeA−) (Supporting Information 1, Tables S1 and S2) [26], which has been widely used for biosynthesis of fungi-derived natural products due to its genetic tractability [27