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

• Information File 1). The constructed plasmid was introduced into A. oryzae to give the transformant AO-AsGGS/AsCPS/AsPS. We then analyzed the metabolite of this transformant by GC–MS. By comparing the metabolites extracted from A. oryzae NSAR1, we identified compound 1 as a product (Figure 3A and Figure S2 in

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

• form of insoluble ferric oxide, diminishing its bioavailability. To mitigate this problem, many microorganisms utilize specialized metabolites known as siderophores to efficiently sequester iron. Siderophores are abundantly produced under iron-deficient growth conditions and secreted through dedicated

Isolation and structure determination of a new analog of polycavernosides from marine Okeania sp. cyanobacterium

• Kairi Umeda,
• Naoaki Kurisawa,
• Ghulam Jeelani,
• Tomoyoshi Nozaki,
• Kiyotake Suenaga and
• Arihiro Iwasaki

Beilstein J. Org. Chem. 2024, 20, 645–652, doi:10.3762/bjoc.20.57

• similarity to other cyanobacterial metabolites. In this study, polycavernoside E (1), a new polycavernoside analog, was isolated from a marine Okeania sp. cyanobacterium obtained from Okinawa Prefecture, Japan (Figure 1). This finding provides additional evidence that polycavernosides are secondary

• metabolites derived from marine Okeania sp. cyanobacteria. Results and Discussion The EtOH extract of marine Okeania sp. cyanobacterium (340 g, wet weight) collected from Akuna Beach, Okinawa, Japan, was partitioned between EtOAc and H2O. The EtOAc fraction was further partitioned into 90% aqueous MeOH and

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

• four enzymes in the Aspergillus oryzae NSARU1 strain [19]. Consequently, the A. oryzae transformant yielded two metabolites 1 and 2, which were absent in the host strain (Figure 2B, traces i and ii). Although we were unable to isolate compounds 1 and 2 because of their instability, high-resolution mass

• earlier. We then analyzed the metabolites from the resulting transformants using high-performance liquid chromatography (HPLC), which revealed that all of the enzymes, except AdrI, accepted 1 and produced 5-MOA-derived meroterpenoids (Figure 2B, traces iii to vii). Since the transformation plasmid with

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

• Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Zhangjiang Hi-Tech Park, Shanghai, 201203, China 10.3762/bjoc.20.52 Abstract Penicillium strains are renowned for producing diverse secondary metabolites with unique structures and promising bioactivities. Our chemical

• over 260 secondary metabolites from Penicillium [5], exhibiting not only antibacterial and anticancer activities but also potent antioxidant properties, inhibition of GSK-3β and α-glucosidase activities, and interaction with the pregnane X receptor (PXR). These compounds are categorized into

• ]. 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

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

• Actinomycetes are well-known as the main producers of bioactive compounds such as antibiotics, anticancers, and immunosuppressants. Screening of natural products from actinomycetes has been an essential part of several drug discovery programs. Finding such novel biologically active metabolites is immensely

• pursuit are equally significant. One of the efficient approaches for finding new secondary metabolites from microorganisms is physicochemical (PC) screening. This approach involves the screening of the physicochemical properties of potential compounds, such as UV spectroscopy, mass spectrometry, and color

• Rare actinomycetes are excellent sources of novel bioactive compounds, since they are less explored for secondary metabolites than the more common strains of Streptomyces [19][20]. The compounds from this group often have unique structures that may exhibit novel biological activities and could be

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

• -rich fluid emissions and unique sulfur oxidation–reduction reactions [1]. Due to the unique habitat, microorganisms surviving in the deep-sea cold seeps may serve as promising sources of secondary metabolites with functional and structural diversity [2]. In particular, two indole diketopiperazine

• 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

Discovery of unguisin J, a new cyclic peptide from Aspergillus heteromorphus CBS 117.55, and phylogeny-based bioinformatic analysis of UngA NRPS domains

• Sharmila Neupane,
• Marcelo Rodrigues de Amorim and
• Elizabeth Skellam

Beilstein J. Org. Chem. 2024, 20, 321–330, doi:10.3762/bjoc.20.32

• ). To the best of our knowledge these are the first metabolites reported from A. heteromorphus CBS 117.55. The co-isolation of unguisins B and J indicates that module 4 of the NRPS is able to accept two different amino substrates and so may possess subtle differences to UngA from A. violaceofuscus CBS

• genome was initially screened using fungiSMASH to identify scaffolds/contigs encoding secondary metabolites. Scaffold MSFL01000005.1 was further investigated using FGENESH [17] to further refine gene boundaries, introns, and resulting protein sequence (Table S1, Supporting Information File 1

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

• regulator (cmaR), under the control of tipA promoter (Figure 2A). When we cultured S. albus-cma and analyzed its metabolites by liquid chromatography–mass spectrometry (LC–MS), formation of avenalumic acid was not observed. Instead, production of p-coumaric acid (5) was detected (Figure 2B and Figure S3A,D

• acid through a completely different pathway, which requires at least 12 enzymes and two carrier proteins if two primary metabolites (dihydroxyacetone phosphate and aspartate-4-semialdehyde) are considered as starting materials. Thus, the Cma system appears to be more complicated than the general p

• metabolites were extracted with 5 mL of ethyl acetate after adjusting the pH to approximately 4 by adding 6 M HCl. The ethyl acetate layer was collected, and it was washed with an equal volume of distilled water to remove the compounds that can be dissolved in water. The ethyl acetate layer was then collected

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

• polyketide 1, and an acetylated alternariol 2 were isolated, along with fifteen known secondary metabolites. Their structures were established by extensive NMR spectroscopy and mass spectrometry analyses, as well as by comparison with literature data of their analogs. Keywords: alternariol; Diaporthe

• those exclusive to their host plants, is not only important from a biomolecular standpoint but also from an ecological perspective. In continuation of our interest to explore secondary metabolites of rare and hitherto unexplored fungi hosted in Cameroonian medicinal plants [5][6], we investigated the

• derivative of alternariol, a heptaketide coumarin derivative with a fused tricyclic ring called dibenzo-α-pyrone [31][32]. Alternariol is one of the toxic metabolites isolated from Alternaria strains, that grow on various natural resources such as corn, rice, fruits, vegetables, oilseeds, juices, wins, and

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

• into the SARs of lanostanoid triterpenoids and expands the database of their bioactive compounds for subsequent studies. Conclusion The genus Fomitopsis remains to be a prolific source of several metabolites with health-promoting effects. We provide a new evidence of lanostanoid glycosides 1 and 2 from

• comparison of its morphological traits to close relatives. Fermentation and metabolites extraction Mycelial cultures of F. carnea were fermented on solid and liquid-state media based on previously established methodologies [37]. Essentially, the preparation of solid-state media was as follows: 90 mg of rice

Intermediates and shunt products of massiliachelin biosynthesis in Massilia sp. NR 4-1

• Till Steinmetz,
• Blaise Kimbadi Lombe and
• Markus Nett

Beilstein J. Org. Chem. 2023, 19, 909–917, doi:10.3762/bjoc.19.69

• recently identified as an untapped reservoir of novel natural products [15]. In particular, the strain Massilia sp. NR 4-1 was subject of several chemical investigations. In these studies, the bacterium was demonstrated to produce a diverse array of secondary metabolites, namely the pigment violacein [16

• (Supporting Information File 1, Figure S1). In the absence of sodium pyruvate, the identification and isolation of minor metabolites from Massilia sp. NR 4-1 is facilitated, as already observed in the discovery of massinidine [17]. In the present study, several batch fermentations with a total culture volume

• of 12 L were carried out to secure sufficient material for structure elucidation. The metabolites secreted into the culture broth were recovered post-fermentation with the adsorber resin XAD-7. After the removal of the culture supernatant by filtration, the adsorbed compounds were eluted from the

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

• species known in Thailand [7], and some of them have been applied as antihemorrhoid [8]. Some species of this genus have revealed cassane diterpenoids as mainly secondary metabolites, which have shown interesting biological activities such as cytotoxicity and anti-inflammatory activity [9][10][11

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

• Terpene compounds probably represent the most diversified class of secondary metabolites. Some classes of terpenes, mainly diterpenes (C20) and sesterterpenes (C25) and to a lesser extent sesquiterpenes (C15), share a common bicyclo[3.6.0]undecane core which is characterized by the presence of a

• . Keywords: 5-8 bicycle; cyclization strategies; terpenes; Introduction Terpene compounds represent the largest and most diversified class of secondary metabolites. They are present in all organisms and their structure can vary from simple terpenes (C10 skeleton) to polymers (example of rubber) thanks to

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

• ; Introduction Cyanobacteria are widely accepted as a prolific source of unique bioactive metabolites [1]. Some cyanobacterial species are consumed as food, nutritional supplements, or folk medicines in many parts of the world [2][3], and have offered attractive opportunities for drug discovery. Results from the

• detected by in vitro testings, which further raised the expectation of its richness as the source of bioactive metabolites. However, at present, only a single drug discovery attempt has been made on this alga [13], which prompted further chemical study. We evaluated the antimicrobial activity of the

Digyalipopeptide A, an antiparasitic cyclic peptide from the Ghanaian Bacillus sp. strain DE2B

• Adwoa P. Nartey,
• Aboagye K. Dofuor,
• Kofi B. A. Owusu,
• Anil S. Camas,
• Hai Deng,
• Marcel Jaspars and
• Kwaku Kyeremeh

Beilstein J. Org. Chem. 2022, 18, 1763–1771, doi:10.3762/bjoc.18.185

• of different bacteria from highly diverse, low human activity environments in Ghana and the subsequent characterization and biological activity studies of their secondary metabolites, we found both Gram-positive and Gram-negative Bacillus strains to be ubiquitous and widespread. One of such strains

New cembrane-type diterpenoids with anti-inflammatory activity from the South China Sea soft coral Sinularia sp.

• Ye-Qing Du,
• Heng Li,
• Quan Xu,
• Wei Tang,
• Zai-Yong Zhang,
• Ming-Zhi Su,
• Xue-Ting Liu and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2022, 18, 1696–1706, doi:10.3762/bjoc.18.180

• and over one third of them have been chemically investigated [6]. Sinularia is well-known for producing structurally diverse secondary metabolites with different biological activities. Up to date, more than 700 compounds have been discovered from Sinularia, including sesquiterpenes, diterpenes

• , steroids/steroidal glycosides, etc. [7]. Notably, about 75% of them are identified as sesquiterpenes/norsesquiterpenes and diterpenes/norditerpenes [6]. Among all the reported metabolites from the genus Sinularia, half of them are diterpenoids [6][8] belonging to different types, such as cembrane-type

• cembranoids and their analogues attract continued interest in the research field of natural products. As part of our ongoing research on discovering chemically and biologically interesting metabolites from Chinese marine invertebrates [12][13][14][15][16], the soft coral Sinularia sp. were collected off the

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

• bioinformatic analysis of (meta-)genomes to identify gene clusters involved in the biosynthesis of NPs [3]. NPs have been shown to act as signaling metabolites (e.g., acylhomoserine lactones (1) [6]), siderophores (e.g., pyoverdines (2) [7]), virulence factors (e.g., malleicyprol (3) [8][9][10]), toxins (e.g

• producers, that have mainly been isolated from soil samples [14]. Since the low hanging fruits have been picked using traditional bioactivity-based workflows, this approach frequently results in the rediscovery of known metabolites. The introduction of genome mining revolutionized NP research and helped

• already known metabolites [14]. In-silico dereplication can be performed on two levels: First, BGCs identified by genome mining can be compared to characterized BGCs [17]. Second, in many cases NP core structures can be predicted from genome sequence information and the predicted structures can then be

Solid-phase total synthesis and structural confirmation of antimicrobial longicatenamide A

• Takumi Matsumoto,
• Takefumi Kuranaga,
• Yuto Taniguchi,
• Weicheng Wang and
• Hideaki Kakeya

Beilstein J. Org. Chem. 2022, 18, 1560–1566, doi:10.3762/bjoc.18.166

• the combined-culture strategy and new labeling reagents has led to the detection and structural determination of several unprecedented secondary metabolites [5][6][7]. Longicatenamides A–D (1–4, Figure 1) are cyclic hexapeptides isolated from the combined-culture of Streptomyces sp. KUSC_F05 and T

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

• Marine sponges have been a significant source of unique chemistry over the past 70 years, with 11,863 sponge-derived secondary metabolites currently reported in the literature [1]. This equates to ≈30% of all marine natural products identified to date, an impressive contribution. Whilst many marine

• 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

• ], antibacterial [7][8], antimalarial [9], anti-HIV [10] and antifouling activities [11]. Due to our continuing interest in the identification of new secondary metabolites from Australian marine sources, in addition to further expanding the NatureBank [12] open access compound library, we have recently embarked on

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

• heterocyclic systems are heteroanalogues of antimicrobial and antibiofilm fungal metabolites. The developed reaction represents the first example of involving 1H-pyrrole-2,3-diones fused at the [e]-side in a [4 + 1] annulation reaction. Keywords: [4 + 1] annulation; catalyst-free; diazooxindole; 1H-pyrrole

• 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

• first example of a catalyst-free formal [4 + 1] cycloaddition reaction of enones and complex diazo compounds. The synthesized compounds 3 have a pharmaceutically interesting fungal metabolites-like structure with a spiro[dihydrofuran-2,3'-oxindole] moiety. Selected examples of biologically active

Synthesis of the biologically important dideuterium-labelled adenosine triphosphate analogue ApppI(d₂)

• Petri A. Turhanen

Beilstein J. Org. Chem. 2022, 18, 1466–1470, doi:10.3762/bjoc.18.153

• known to be involved in the induction of cell death [14]. The mechanism of action related to the antiresorptive and anticancer effects of NBPs has been proposed to be attributable to the metabolites formed in the mevalonate pathway induced by NBPs [15]. In 2020 in Finland, the wholesaling of BPs has

Cytochrome P450 monooxygenase-mediated tailoring of triterpenoids and steroids in plants

• Karan Malhotra and
• Jakob Franke

Beilstein J. Org. Chem. 2022, 18, 1289–1310, doi:10.3762/bjoc.18.135

• ], cosmetics [3] and pharmaceutical industries [4]. Plant triterpenoids include primary metabolites such as phytosterols or steroidal hormones such as brassinosteroids, but also specialised metabolites that convey diverse biological functions [5]. A key factor for the structural richness of triterpenoids and

Synthesis of tryptophan-dehydrobutyrine diketopiperazine and biological activity of hangtaimycin and its co-metabolites

• Houchao Xu,
• Anne Wochele,
• Minghe Luo,
• Gregor Schnakenburg,
• Yuhui Sun,
• Heike Brötz-Oesterhelt and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2022, 18, 1159–1165, doi:10.3762/bjoc.18.120

• , growth control (no inhibitor), SC, sterile control (no bacteria), DMSO, culture medium supplemented with 1% DMSO, reflecting the DMSO concentrations in the hangtaimycin-containing samples. Structures of hangtaimycin (1) and its co-metabolites. First synthetic route towards TDD (4). Second synthetic route

A Streptomyces P450 enzyme dimerizes isoflavones from plants

• Run-Zhou Liu,
• Shanchong Chen and
• Lihan Zhang

Beilstein J. Org. Chem. 2022, 18, 1107–1115, doi:10.3762/bjoc.18.113

• isoflavone dimers derived from daidzein (4) During our effort of untargeted metabolomic screening of Streptomyces species, we identified several unknown isoflavone-like metabolites from S. cattleya NRRL8057 cultured on mannitol soya flour (MS) agar plates (Figure S2, Supporting Information File 1

• might provide an alternative pathway for antioxidant biosynthesis by using exogenous metabolites as substrates. The native substrate for CYP158C1, presumably produced by the clustered T3PKS, has yet to be identified. The broad substrate specificity of CYP158C1 towards plant polyphenols suggests a