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

• ; 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

• extract, pH 6.3) by the endophytic fungus Dendrothyrium variisporum. This fungus, isolated from the roots of the Algerian plant Globularia alypum, was explored for the first time for its potential to produce secondary metabolites [16]. Despite the abundant production of massarilactone D, it did not

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

• 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

• acid derivative named farinosone D. In addition, five known secondary metabolites were identified based on HRESIMS and detailed 1D/2D NMR spectroscopic analyses along with comparison with the reported literature. The isolated compounds were differentiated into two 2-pyridone derivatives farinosones A

Ceratinadin G, a new psammaplysin derivative possessing a cyano group from a sponge of the genus Pseudoceratina

• Shin-ichiro Kurimoto,
• Kouta Inoue,
• Taito Ohno and
• Takaaki Kubota

Beilstein J. Org. Chem. 2024, 20, 3215–3220, doi:10.3762/bjoc.20.267

• , the first asymmetric total synthesis of psammaplysin A was accomplished by Smith and Morrow, and the absolute configuration of compound 1 was also confirmed through organic synthesis [7]. In our ongoing research focused on uncovering new bioactive secondary metabolites from Okinawan marine sponges, we

Discovery of ianthelliformisamines D–G from the sponge Suberea ianthelliformis and the total synthesis of ianthelliformisamine D

• Sasha Hayes,
• Yaoying Lu,
• Bernd H. A. Rehm and
• Rohan A. Davis

Beilstein J. Org. Chem. 2024, 20, 3205–3214, doi:10.3762/bjoc.20.266

• and fauna have evolved over billions of years to survive within this unique environment [1][2], which has led to the production and diversification of unique and novel metabolites with specialised biological functions [3][4]. The richest diversity of marine metabolites are derived from invertebrates

• ; most of which are sessile and lack the ability to physically defend themselves from both predators and competitors and thus rely on chemical mechanisms for their defense [1]. Metabolites derived from marine sponges contribute more than half of all compounds identified from marine invertebrates [1][5

• ], therefore it is no surprise that sponges are highly sought after for novel bioactive metabolites and have been a major focus of marine natural product drug discovery for over 70 years. The identification of ianthelliformisamines A–C from the Australian marine sponge Suberea ianthelliformis, which displayed

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

• ingredient(s) and their mechanisms of action, humans have taken advantage of the therapeutic effects of herbal and microbial extracts for thousands of years [1]. We now know that natural products, genetically encoded secondary metabolites, are in most cases responsible for the desirable effects in these

• would be fractionated further, tested again, and this process would be performed iteratively until a pure compound is obtained. Notably, BGF is not limited to the identification of metabolites with antimicrobial activity or those of bacterial origin. It is applicable to the screening of natural products

• bioinformatic analysis. Their updated PRISM 4 pipeline outperformed antiSMASH5 and was able to predict the chemical structures of a wide variety of secondary metabolites [90]. Notably, the repertoire of PRISM 4 spans beyond NRPs and PKs and includes alkaloids, terpenoids, aminoglycosides, nucleosides, etc

Tailored charge-neutral self-assembled L₂Zn₂ container for taming oxalate

• David Ocklenburg and
• David Van Craen

Beilstein J. Org. Chem. 2024, 20, 3007–3015, doi:10.3762/bjoc.20.250

• ; metallocontainer; oxalate; Introduction Dicarboxylic acids and their corresponding anions are essential intermediates in the biosynthesis of proteins and important biological metabolites [1][2]. As a result, the development of receptors for this class of compounds is of high interest [3][4][5]. Oxalate, the

Young investigators in natural products chemistry, biosynthesis, and enzymology

• Jeffrey D. Rudolf,
• Lena Barra and
• Takayoshi Awakawa

Beilstein J. Org. Chem. 2024, 20, 2720–2721, doi:10.3762/bjoc.20.229

• structural elucidation of a single natural product can inspire a wide array of scientific disciplines. Natural products, first as bioactive metabolites in traditional medicines and now as isolated or (bio)synthesized metabolites, are one of the most important sources of therapeutics historically and today

Transition-metal-free decarbonylation–oxidation of 3-arylbenzofuran-2(3H)-ones: access to 2-hydroxybenzophenones

• Bhaskar B. Dhotare,
• Seema V. Kanojia,
• Chahna K. Sakhiya,
• Amey Wadawale and
• Dibakar Goswami

Beilstein J. Org. Chem. 2024, 20, 2655–2667, doi:10.3762/bjoc.20.223

• UV-protector, or its metabolites, have been associated with estrogenic activities [7]. A further structure–activity relationship study revealed that a 5-substitution decreases estrogenic activity. Similar results were obtained in another study where 2-hydroxy-5-methylbenzophenone was found to exhibit

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

• investigated by direct inlet atmospheric solids analysis probe-atmospheric mass spectrometry (ASAP-APCI-MS), which allows the detection of secondary metabolites up to a molecular mass of 1,500 Da, but no additional compounds were detected. A more detailed description of the use of this method in natural

Applications of microscopy and small angle scattering techniques for the characterisation of supramolecular gels

• Connor R. M. MacDonald and
• Emily R. Draper

Beilstein J. Org. Chem. 2024, 20, 2608–2634, doi:10.3762/bjoc.20.220

Photoredox-catalyzed intramolecular nucleophilic amidation of alkenes with β-lactams

• Valentina Giraldi,
• Giandomenico Magagnano,
• Daria Giacomini,
• Pier Giorgio Cozzi and
• Andrea Gualandi

Beilstein J. Org. Chem. 2024, 20, 2461–2468, doi:10.3762/bjoc.20.210

• well known as a potent β-lactamase inhibitor [33][34]. It is produced by the filamentous bacterium Streptomyces clavuligerus, but in low yield. Various clavams 2–5 have been identified (Figure 2B), either through isolation as natural metabolites or obtained by synthetic methods [35][36][37][38][39][40

Natural resorcylic lactones derived from alternariol

• Joachim Podlech

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

• 9-O-methyl ether, altenusin, dehydroaltenusin, altertenuol, and altenuene) were frequently found and isolated as fungal contaminants in food and feed and have been investigated in significant detail, further metabolites, which were much more rarely found as natural products, similarly show

• 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

• . Derivatives formed through metabolization in the human body (or in animals) are only covered if the respective metabolites were similarly identified as natural products. A thorough survey of the literature revealed (at now) 127 natural products to be classified as natural resorcylic lactones derived from

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

• metabolites, and most of them are pyrroloterpenes from Streptomyces (Figure 1 and Figure S54 in Supporting Information File 1). Examples include pyrrolostatin [12] and its congener geranylpyrrol A [13], bearing a carboxylic group at the C2 and a geranyl group at the C4 position of the pyrrole ring, and their

• a fermentation extract of Allostreptomyces sp. RD068384, a strain belonging to an almost unstudied actinomycetes genus within the family Streptomycetaceae. Compounds 1–5 are characterized by a pyrrole-2-carboxylic acid core decorated with a formyl group and an alkyl side chain. Secondary metabolites

• and carboxyl functionalities. Furthermore, a β-alkyl substitution is not very common in pyrrolic secondary metabolites. The most related metabolites to 1–5 are the reported alkylpyrroles from a marine sponge Oscarella lobularis [7] and pyrroloterpenes from Streptomyces [12][13][14][15], although the

Discovery of antimicrobial peptides clostrisin and cellulosin from Clostridium: insights into their structures, co-localized biosynthetic gene clusters, and antibiotic activity

• Moisés Alejandro Alejo Hernandez,
• Katia Pamela Villavicencio Sánchez,
• Rosendo Sánchez Morales,
• Karla Georgina Hernández-Magro Gil,
• David Silverio Moreno-Gutiérrez,
• Eddie Guillermo Sanchez-Rueda,
• Yanet Teresa-Cruz,
• Brian Choi,
• Armando Hernández Garcia,
• Alba Romero-Rodríguez,
• Oscar Juárez,
• Siseth Martínez-Caballero,
• Mario Figueroa and
• Corina-Diana Ceapă

Beilstein J. Org. Chem. 2024, 20, 1800–1816, doi:10.3762/bjoc.20.159

• genes and genomes across diverse species and populations. This provides insights into the origins and evolution of genes that have evolved as "tools" in the ongoing biological battles in the microbial world. The biodiversity of specialized metabolites is strain-specific, meaning that even closely

• related organisms can have distinct metabolic capabilities. Consequently, researchers can unveil new clusters and metabolites by tracking the conserved genes participating in biosynthetic processes. In recent years, notable achievements have been seen in genome mining in discovering antimicrobial

• the Clostridium genus encountered 17 protein sequences associated with 12 genomes. After analyzing these genomes with AntiSMASH [3], we identified 150 different BGCs of specialized metabolites from different biosynthetic classes. The RiPPs accounted for 36% of these (54 clusters). A total of 14 BGCs

Harnessing unprotected deactivated amines and arylglyoxals in the Ugi reaction for the synthesis of fused complex nitrogen heterocycles

• Javier Gómez-Ayuso,
• Pablo Pertejo,
• Tomás Hermosilla,
• Israel Carreira-Barral,
• Roberto Quesada and
• María García-Valverde

Beilstein J. Org. Chem. 2024, 20, 1758–1766, doi:10.3762/bjoc.20.154

• piperazinoquinazoline derivatives, a core found in fungal metabolites [25][26], systems with promising antitumour activity [27], as well as dipyrrolopiperazinone derivatives, substructure found in some alkaloids such as dibromophakellin or the palau’amine [28], which possess immunosuppressive and cytotoxic properties

Synthesis of polycyclic aromatic quinones by continuous flow electrochemical oxidation: anodic methoxylation of polycyclic aromatic phenols (PAPs)

• Hiwot M. Tiruye,
• Solon Economopoulos and
• Kåre B. Jørgensen

Beilstein J. Org. Chem. 2024, 20, 1746–1757, doi:10.3762/bjoc.20.153

• alternative to classical synthesis [25][26][27][28]. Electrochemical oxidation reactions are further used to emulate enzymatic oxidations of drugs and explore potential metabolites [29][30][31]. Electrochemical flow systems provide fast electrosynthesis with low cell resistance, large electrode area, and good

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

• 1970s, the biosynthetic pathway of 4 has been investigated through isotope labelling and analysis of metabolites from S. fradiae mutants [70][71][72][73]. Heterologous production of 4 was also achieved by expression of elucidated biosynthetic gene cluster from S. fradiae in Streptomyces venezuelae [74

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

• modifications have been observed during the maturation of different RiPPs. One example is the biosynthesis of thiopeptide GE2270, which is produced by the actinomycete Planobispora rosea ATCC53733 as a complex of related metabolites that differ in the number of methyl groups installed on the macrocyclic core

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

• -Hydroxybenzoate esters The first group of secondary metabolites described from the genus Microbulbifer were 4-hydroxybenzoate (4HBA, 1) and three alkyl esters (butyl, heptyl, and nonyl, 2–4, Figure 6). Commonly known as parabens, these molecules were isolated from a tropical ascidian-derived Microbulbifer sp. A4B

• thus so far is not comparable to the expected metabolites envisioned from bioinformatics analyses of the Microbulbifer genomes. Contemporary and in-development tools and technologies for data mining, synthetic biology, and strain manipulation will have a transformative effect on future natural product

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

• . ameranicus using UHPLC-HRMS/MS. Finally, we generated a global natural product social (GNPS) network to show the correlation between metabolites from these different plant species (Figure 5) [29]. Cyclopeptides in Ceanothus americanus The GNPS network showed the presence of multiple features from C

A Diels–Alder probe for discovery of natural products containing furan moieties

• Alyssa S. Eggly,
• Namuunzul Otgontseren,
• Carson B. Roberts,
• Amir Y. Alwali,
• Haylie E. Hennigan and
• Elizabeth I. Parkinson

Beilstein J. Org. Chem. 2024, 20, 1001–1010, doi:10.3762/bjoc.20.88

• . Natural products with furan moieties can also be signaling hormones. Methylenomycin furans (MMFs) are naturally occurring secondary metabolites that are produced by Streptomyces coelicolor, a soil dwelling bacterium. These molecules are important as they induce the production of the antibiotic

• solely based on which alkyl chain is present at the two position [7]. Based on genomic data, it is hypothesized that other secondary metabolites similar to the MMFs exist in other strains of actinobacteria. However, it is time-intensive and challenging to isolate and elucidate novel natural products

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

• originated from two key C5 building blocks, namely isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP), which are biosynthesized via either the methylerythritol phosphate (MEP) pathway or the mevalonic acid (MVA) pathway by using the primary metabolites. Different numbers of IPP and DMAPP

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

• ), 2α-hydroxydrimenol (3), and 3-ketodrimenol (4) (Figure 2a). HPLC analysis of metabolites from different culture media showed that YMS medium was more conducive to produce compound 3 (Figure 2b and Table S1 in Supporting Information File 1). The chemical structures of these isolated compounds were

• . (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

• Streptomyces strains, with S. avermitilis SUKA22 harboring the empty pSET152 vector as the control. (d) HPLC analysis of metabolites co-expressed with drimenyl diphosphate synthases (CavC), Nudix hydrolase (CavB), and one of the P450s, either CavA (DL10089), CavE (DL10090), or CavG (DL10091). Substrate scope

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

• Shun Saito Midori A. Arai Department of Biosciences and Informatics, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan 10.3762/bjoc.20.69 Abstract Secondary metabolites produced by actinomycete strains undoubtedly have great potential for use in applied research areas such as

• drug discovery. However, it is becoming difficult to obtain novel compounds because of repeated isolation around the world. Therefore, a new strategy for discovering novel secondary metabolites is needed. Many researchers believe that actinomycetes have as yet unanalyzed secondary metabolic activities

• , and the associated undiscovered secondary metabolite biosynthesis genes are called “silent” genes. This review outlines several approaches to further activate the metabolic potential of actinomycetes. Keywords: actinomycete; co-culture; heat shock metabolites (HSMs); secondary metabolites; silent

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

• -II (2b). Through subcellular localization analysis, they proposed that the biosynthesis of crocins initiates in the plastids. The metabolites are transported to the endoplasmic reticulum and cytoplasm and are stored in the vacuole. Moreover, they confirmed that the ABC transporter is involved in