Article

17-Hydroxycyclooctatin, a Fused 5-8-5 Ring Diterpene, from Streptomyces sp. MTE4a

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Abstract

A new diterpene with a fused 5-8-5 ring system was isolated from the fermentation broth of a soil actinomycete. The stereochemistry at C-15 was determined in an unusual manner using a decomposition product.

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... Additionally, 17-hydroxycyclooctatin was isolated from Streptomyces sp. MTE4a (4). To date, only four compounds with this novel 5-8-5-fused ring backbone have been isolated thus far. ...
... The 1 H and 13 C NMR spectra of 2 closely resembled Cyclooctatins have a unique tricyclic diterpene skeleton (C 20 ) characterized by a 5-8-5-fused ring system. Prior to the current study, only four compounds of this type were identified, including cyclooctatin (2), cyclooctat-9-en-7-ol, cyclooctat-9-en-5,7-diol (3), and 17-hydroxycyclooctatin (4). Previous studies suggested that cyclooctatin was a potent inhibitor of lysophospholipase and exhibited no significant antimicrobial activity at 100 μg/mL (1). ...
... Additionally, 17-hydroxycyclooctatin was isolated from Streptomyces sp. MTE4a (4). To date, only four compounds with this novel 5-8-5-fused ring backbone have been isolated thus far. ...
... The 1 H and 13 C NMR spectra of 2 closely resembled Cyclooctatins have a unique tricyclic diterpene skeleton (C 20 ) characterized by a 5-8-5-fused ring system. Prior to the current study, only four compounds of this type were identified, including cyclooctatin (2), cyclooctat-9-en-7-ol, cyclooctat-9-en-5,7-diol (3), and 17-hydroxycyclooctatin (4). Previous studies suggested that cyclooctatin was a potent inhibitor of lysophospholipase and exhibited no significant antimicrobial activity at 100 μg/mL (1). ...
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Genome sequence analysis of Streptomyces sp. LZ35 has revealed a large number of secondary metabolite pathways, including a complete gene cluster for the biosynthesis of cyclooctatin. This cluster contains four genes, cotB1-4, located in a 5-kb region. Optimization of fermentation medium for LZ35Δheng (SR107) led to the identification of cyclooctatin (1) and 16,17-dihydroxycyclooctatin (2), a new diterpene. The structures of these substances were elucidated on the basis of 1D-, 2D-NMR, and HRESIMS data. Cytotoxicity against MDA-MB-231 and A549 cell lines was also evaluated. Results demonstrated that gene cluster and pathway analysis are key to guided isolation of new natural products.
... They were first isolated as glycosides from the phytopathogenic fungus Fusicoccum amygdali, in 1964 [81]. Substances exhibiting this structural motif have been isolated from a variety of sources including fungi such as Talaromyces purpureogenus, Alternaria brassicicola XXC, and Trichoderma citrinoviride cf-27 ( Figure 3), and rarely from liverworts, algae, ferns, streptomycetes, and higher plants, some of which showed remarkable biological effects relevant for drug discovery, such as antibacterial, antitumor, anti-inflammatory, and antifungal activities [82][83][84][85][86][87][88][89]. A new diterpenoid roussoellol C 26 that exhibited moderate antiproliferative activities against human breast adenocarcinoma (MCF-7) cell line with an IC50 value of 6.5 μM has been isolated from an extract of laboratory cultures of the marine-derived fungus Talaromyces purpurogenus [90]. ...
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Fungi have traditionally been a very rewarding source of biologically active natural products, while diterpenoids from fungi, such as the cyathane-type diterpenoids from Cyathus and Hericium sp., the fusicoccane-type diterpenoids from Fusicoccum and Alternaria sp., the guanacastane-type diterpenoids from Coprinus and Cercospora sp., and the harziene-type diterpenoids from Trichoderma sp., often represent unique carbon skeletons as well as diverse biological functions. The abundances of novel skeletons, biological activities, and biosynthetic pathways present new opportunities for drug discovery, genome mining, and enzymology. In addition, diterpenoids peculiar to fungi also reveal the possibility of differing biological evolution, although they have similar biosynthetic pathways. In this review, we provide an overview about the structures, biological activities, evolution, organic synthesis, and biosynthesis of diterpenoids that have been specially produced by fungi from 2010 to 2020. We hope this review provides timely illumination and beneficial guidance for future research works of scholars who are interested in this area.
... The presence of N-acyl homoserine lactones (AHLs) mediated QS in sponge extracts, sponge-bacterial isolates and a metagenomics-derived genome of a sponge symbiont [e.g., 23,24,26,27,28] are well documented. Few studies have searched for QSI compounds in sponges and their isolates, mainly in a biotechnological context, as such molecules could provide alternatives for antimicrobials, and presence of QSI molecules was reported [29][30][31][32][33]. Whilst AHLs have a common structure, QSI compounds are way more variable: from being structurally similar to AHLs [34,35] to cyclic peptides [36][37][38], alkaloids [31,39], lactones [23,40] and diterpenes [41][42][43]. In our recent work, a novel lactone, named plakofuranolactone, which showed a strong QSI activity at submicromolar concentration, has been discovered from the extract of the Indonesian sponge Plakortis cf. ...
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Marine sponges, a well documented prolific source of natural products, harbors numerous microbial communities believed to possess N-acyl homoserine lactones (AHLs) mediated Quorum sensing (QS) as one of the mechanisms of interaction. Bacteria and eukaryotic organisms are known to produce molecules that can interfere with QS signaling, thus affecting microbial genetic regulation and function. In the present study, we established the potential for production of both QS signal molecules as well as QS interfering molecules (QSI) in the same sponge species Sarcotragus spinosulus. A total of eighteen saturated acyl chain AHLs were identified along with six putative unsaturated acyl chain AHLs. Bioassay guided purification led to the isolation of two brominated metabolites with QS-interfering activity. The structures of these compounds were elucidated by comparative spectral analysis of 1HNMR and HR-MS data and was identified as 3-Br-N-methyltyramine (1) and 5,6-dibromo-N,N-dimethyltryptamine (2). The QSI activity of compounds 1 and 2 were evaluated using reporter gene assays for long- and short-chain signals (E. coli pSB1075 and E. coli pSB401) and was confirmed by measuring dose dependent inhibition of proteolytic activity and pyocyanin production in P. aeruginosa PAO1. The obtained results showed the co-existence of QS and QSI in S. spinosulus, a complex network which may mediate the orchestrated function of the microbiome within the sponge holobiont.
... Fusicoccane diterpenoids usually possessing a tricyclic (5-8-5) ring system (such as brassicicenes, cyclooctatins, fusicoccins, and periconicins) are biogenetically generated from geranylgeranyl diphosphate (GGDP) 18 , which are found from various natural sources, including bacteria 19,20 , fungi [21][22][23][24] , liverworts 25,26 , algas 27 , and higher plants 28,29 . Fusicoccane diterpenoids exhibit diverse biological activities, such as plant growth regulating activity (fusicoccins) 30 , lysophospholipase inhibitory activity (cyclooctatin) 31 , antimicrobial activity (periconicins) 32,33 , nitrification inhibitory activity (brachialactone) 34 , cytotoxicity against tumor cells (cotylenins) 35 , inhibiting insulin-stimulated GLUT4 fusion activity (fusicoccins) 35 , and so ...
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Riassunto Con l'uso combinato di metodi chimici, spettroscopici, e di strutturistica chimica diffrattometrica è stato possibile assegnare la struttuta I alla fusicoccina A, metabolita fitopatogeno del fungoFusicoccum amygdali Del.
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  • Cm Waters
  • Bl Bassler
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