Semisynthetic derivatives of massarilactone D with cytotoxic and nematicidal activities

• Rémy B. Teponno,
• Sara R. Noumeur and
• Marc Stadler

Beilstein J. Org. Chem. 2025, 21, 607–615, doi:10.3762/bjoc.21.48

• Massarilactones constitute a rare class of polyketides produced mainly by endophytic fungi. Given that semisynthetic derivatives often exhibit biological activities greater than those of the substrates, seven previously unreported derivatives of massarilactone D, compounds 2–8, were synthetized by acylation with

• ; nematicidal activity; Introduction Cancer continues to be responsible for morbidity and mortality all over the world. Endophytic fungi have been shown to be an important source of secondary metabolites endowed with interesting cytotoxic activities. However, resistance to cancer therapies is a persistent

• products can serve as effective scaffold for the design and synthesis of derivatives with improved biological activities [5][6][7]. Massarilactones are produced by marine and endophytic fungi and bear close biogenetic similarity to several other fungal PKS1-derived metabolites including rosigenin, the

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

• 10.3762/bjoc.21.23 Abstract During the course of our studies on the secondary metabolism of rare, hitherto untapped Thai insect-associated fungi, the ethyl acetate (EtOAc) extract derived from solid-state cultivation of Samsoniella aurantia on rice afforded one previously undescribed tetramic acid

• exacerbates healthcare and economic burdens, thereby prompting the urgent need for novel therapeutic strategies and antibiofilm agents. During our ongoing research targeting potential antibiofilm metabolites from fungi, we explored entomopathogenic species such as those belonging to the genera Beauveria and

• Metarhizium that are known as biocontrol agents against insect pests like mosquitoes and ticks in agricultural and forestry applications [5]. Secondary metabolites produced by entomopathogenic fungi have garnered attention due to their diverse biological activities, encompassing antimicrobial, antiviral, and

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

Natural resorcylic lactones derived from alternariol

• Joachim Podlech

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

• fungi, are discussed with view on their isolation, structure, biological activities, biosynthesis, and total syntheses. This class of compounds consists until now of 127 naturally occurring compounds, with very divers structural motifs. Although only a handful of these toxins (i.e., alternariol and its

• discussed resorcylic lactones) are predominantly, but by far not exclusively, isolated from Alternaria spp., especially from Alternaria alternata. The genus Alternaria in the family Pleosporaceae (Pleosporales, Dothideomycetes, Ascomycota) belongs to the fungi imperfecti and all species are known as plant

• botrallin (77; vide infra) [36][37]. While no further report on graphislactone B was published, graphislactone A was furthermore isolated from various fungi: from Microsphaeropsis olivacea [167], Cephalosporium acremonium [168], and a further C. sp. [169], from Coniothyrium sp. [170], from Rhizopycnis vagum

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

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

Syntheses and medicinal chemistry of spiro heterocyclic steroids

• Laura L. Romero-Hernández,
• Ana Isabel Ahuja-Casarín,
• Penélope Merino-Montiel,
• Sara Montiel-Smith,
• José Luis Vega-Báez and
• Jesús Sandoval-Ramírez

Beilstein J. Org. Chem. 2024, 20, 1713–1745, doi:10.3762/bjoc.20.152

• thermophilum and Thermomyces lanuginosus fungi. The activity was related to the presence of fluorine atoms, and the substitution of -NH with trifluoroacetyl group achieved the most active compound. Spirothiadiazine steroids Novel steroidal spiro-1,3,4-thiadiazines have been recently described through a one-pot

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

• hydroxy group of the aglycon. Cotylenin exhibits promising anticancer activity, and its diterpene aglycon, cotylenol (1), was isolated from the filamentous fungi such as Phomopsis amygdali and Cladosporium sp. 501-7W (Scheme 2A) [20][21][22]. Brassicicenes, differing in oxidation levels from 1, have been

• brassicicenes 27–29. In situ generation of highly reactive intermediates: trichodimerol and the bisorbicillinoid family The bisorbicillinoid family, isolated from fungi such as Penicillium chrysogenum, has dimeric intricate scaffolds, as exemplified by trichodimerol (2) (Scheme 4) [28][29]. The biosynthetic

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

• the specialised metabolism of bacteria and fungi. Each NRPS module is minimally composed of a condensation (C) domain, an adenylation (A) domain, and a peptidyl carrier protein (PCP or thiolation/T domain), and one module typically incorporates one amino acid into the final natural product. In

• of core peptide sequences [100][101]. Type IV borosins are more distantly related homologues found in bacteria; although it was originally believed that borosins occur mainly in fungi, Cho et al. and Imani et al. both demonstrated that type IV borosin BGCs are widespread in bacteria and have

• almost always show Asn4 methylation. Further investigation into the substrate scope of PbtM1 would be interesting to determine its potential in peptide engineering [64]. An example for lysine N-methylation can be found in epichloëcyclins. This family of RiPPs is found in endophytic fungi of the genus

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

• -linked homopolymer of N-acetyl-β-ᴅ-glucosamine (GlcNAc), the second most abundant biomass on earth after cellulose (Figure 4). Approximately 1011 tons of chitin are produced annually in nature, about 70% of which originate from the ocean. Most of the chitin is recycled by bacteria and fungi as carbon and

• Gram-positive bacteria Kocuria rhizophila and S. aureus, Gram-negative bacterium Tenacibaculum maritimum, and a panel of fungi. These molecules also demonstrated moderate cytotoxicity against P388 murine leukemia cells. The bisindole alkaloid violacein (24, Figure 8) was isolated and characterized from

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

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