New bioactive metabolites isolated from the endophytic fungus Stemphylium globuliferum isolated from Mentha pulegium growing in Morocco

Debbab, Abdessamad; Edrada, Ru Angelie; Wray, Victor; Müller, Wieland; Hakiki, A.; Mosaddak, M.; Proksch, Peter; Ebel, Rainer

doi:10.1055/s-2007-986734

Cited by 31 publications

(43 citation statements)

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“…Nataloe-emodin 10 dimers with alternative aryl-aryl bonds have not been observed in C. fulvum, and they do not have dimeric forms of emodin 5, which suggests that ClaM might be highly selective for both substrate and type of linkage that it catalyzes. In contrast, Alternaria species produce a large variety of alterporriol compounds, which are heterodimers of macrosporin and altersolanol exhibiting various couplings, including C5-C5′, C1-C7′, C7-C5′, and C2-C2′ bonds (28,33). Homodimers of macrosporin or altersolanol were also isolated and show C4-C6′ and C4-C8′ bonds (28).…”

Section: Discussionmentioning

confidence: 99%

Elucidation of cladofulvin biosynthesis reveals a cytochrome P450 monooxygenase required for anthraquinone dimerization

Griffiths

Mesarich

Saccomanno

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

161

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Anthraquinones are a large family of secondary metabolites (SMs) that are extensively studied for their diverse biological activities. These activities are determined by functional group decorations and the formation of dimers from anthraquinone monomers. Despite their numerous medicinal qualities, very few anthraquinone biosynthetic pathways have been elucidated so far, including the enzymatic dimerization steps. In this study, we report the elucidation of the biosynthesis of cladofulvin, an asymmetrical homodimer of nataloe-emodin produced by the fungus Cladosporium fulvum. A gene cluster of 10 genes controls cladofulvin biosynthesis, which begins with the production of atrochrysone carboxylic acid by the polyketide synthase ClaG and the β-lactamase ClaF. This compound is decarboxylated by ClaH to yield emodin, which is then converted to chrysophanol hydroquinone by the reductase ClaC and the dehydratase ClaB. We show that the predicted cytochrome P450 ClaM catalyzes the dimerization of nataloe-emodin to cladofulvin. Remarkably, such dimerization dramatically increases nataloe-emodin cytotoxicity against mammalian cell lines. These findings shed light on the enzymatic mechanisms involved in anthraquinone dimerization. Future characterization of the ClaM enzyme should facilitate engineering the biosynthesis of novel, potent, dimeric anthraquinones and structurally related compound families.secondary metabolism | gene cluster | cytoxicity | emodin | nataloe-emodin

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Section: Discussionmentioning

confidence: 99%

Elucidation of cladofulvin biosynthesis reveals a cytochrome P450 monooxygenase required for anthraquinone dimerization

Griffiths

Mesarich

Saccomanno

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

161

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“…China at the middle of July 2011. The endophytic fungus was isolated from the healthy leaves of related plant by using procedure previously described (Debbab et al 2009). A strain (strain designation is AMCL7) is kept in of the author´s laboratory (P.P).…”

Section: Methodsmentioning

confidence: 99%

New Natural Product from Botryosphaeria australis, an Endophyte from Mangrove Avicennia marina

Bara

Zerfaß

Lai

et al. 2013

Squalen Bull. Marine Fisheries Postharvest Biotech.

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Chemical investigation of the endophytic fungus Botryosphaeria australis isolated from Avicennia marina originally from Hainan Province, P.R. China, yielded a new compound botryosphaenin (1), from the class of napthoquinone, together with 5 known compounds, botryosterpene (2) and 5-hydroxy-2,7-dimethoxynaphthalene-1,4-dione (3) and its derivatives, 6-ethyl-5-hydroxy-2,7-dimethoxynaphthalene-1,4-dione (4), O-methylaspmenone (5), Omethylasparvenone (6) and 5-(carboxymethyl)-7-hydroxy-1,4a-dimethyl-6-methylene decahydron aphthalene-1-carboxylic acid (7). Their structures were determined on the basis of spectroscopic methods including 1D ( 1 H, 13 C, and DEPT) and 2D (COSY, HMQC, HMBC, and ROESY) NMR experiments and by mass spectroscopic measurements The new compounds, 1 showed activity against the bacterial pathogens Staphylococcus aureus, several Streptococcus species and Bacillus subtilis, but also against the eukaryotic cell lines THP-1 (human leukemia monocyte) and BALB/3T3 (mouse embryonic fibroblast). Keywords: Mangrove, Avicennia marina, Botryosphaeria australis, antibiotic activities, cytotoxicity ABSTRAK Telah dilakukan penelitian kimiawi tentang jamur endofit Botryosphaeria australis yang diisolasi dari bakau Avicennia marina yang tumbuh di kawasan Provinsi Hainan, Republik Rakyat China. Dari penelitian ini diperoleh senyawa botryosphaenin (1), yang merupakan senyawa baru , dari kelas napthoquinone , bersama dengan lima senyawa yang diketahui sebelumnya yaitu, botryosterpene (2) dan 5 -hidroksi -2,7 -dimetoksinaftalen -1 ,4 -dion (3) dan turunannya , 6 -etil -5 -hidroksi -2 ,7 -dimetoksinaftalen -1 ,4 -dion (4) , O -metilaspmenon (5) , O -metilasparvenon (6) dan 5 -( karboksimetil ) -7 -hidroksi -1 , asam 4a -dimetil -6 -1 -metilendekahidronaftalen karboksilat (7). Strukturnya kimia dari senyawa-senyawa tersebut di atas ditentukan berdasarkan analisis spektroskopi Resonansi Magnetik Inti (NMR) termasuk 1D (1H , 13C, dan DEPT) dan 2D ( COSY, HMQC, HMBC, and ROESY) serta menggunakan spektroskopi massa. Senyawa baru yang diisolasi (1) tidak hanya menunjukkan aktivitas yang kuat melawan bakteri patogen Staphylococcus aureus, beberapa spesies Streptococcus dan Bacillus subtilis, tetapi juga terhadap galur sel eukariotik THP -1 (human leukemia monocyte) dan BALB/3T3 (mouse embryonic fibroblast) .

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“…Pure strains were isolated by repeated inoculation. The purified fungus was later transferred to the liquid medium for scaling up 14 .…”

Section: Isolation Of the Endophytesmentioning

confidence: 99%

“…Culture media and mycelia were then homogenized in the Ultraturrax for 10 min for cell destruction, followed by vacuum filtration using a Buchner funnel. The mycelium residue was discarded while EtOAc culture filtrates were collected, pooled, dried under vacuum, suspended in 200 mL H2O and extracted with EtOAc (3 x 200 mL) using a separating funnel 14 .…”

Section: Medium Scale Fermentation Extraction and Isolationmentioning

confidence: 99%

Metabolomics and Bioactivity Guided Isolation of Secondary Metabolites from the Endophytic Fungus Chaetomium sp.

Tawfik

Tawfike

Abdo

et al. 2017

Journal of Advanced Pharmacy Research

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Objectives: the aim of this study is to explore the secondary metabolites produced by the endophytic fungus Chaetomium sp. isolated from Scencio stapeliiformis (E.Phillips) as well as investigate the anticancer and antimicrobial activity of crude extracts, fractions and pure compounds. Methods: An endophytic fungus (Chaetomium sp.) was isolated from the arial part of S. stapeliiformis (from Giza, Egypt). DNA sequencing analysis, morphological and chemotaxonomy investigations were used for taxonomic identification. Metabolomics tools and dereplication studies were employed to choose the optimum growth medium and conditions that produce the most significant metabolites. The crude extract of the optimal fungal culture of Chaetomium sp. was then fractionated using flash chromatography and medium pressure liquid chromatography (MPLC). The structure of the isolated compounds was determined on the basis of 1D, 2D NMR and mass spectrometry (HR-ESIMS) analysis. Results: The Metabolomics and bioassay-guided isolation afforded five pure compounds; p-hydroxybenzaldehyde (1), Uracil (2), 3-benzyl-6-isobutyl piperazine-2,5-dione (3), Cyclo (L-Alanin-Lleucin) (4) and Cyclo-(L-proline-L-leucine) (5). Multivariate data analysis highlighted the most significant metabolites contributed to the measured bioactivity. All fungal extracts were tested for the anticancer activity but extract of 30 days liquid culture of Chaetomium showed the most anticancer activity. The pure compounds were tested for their anticancer and antimicrobial activities. Compounds 3 and 5 exhibited a significant anti-trypanosomal activity while compounds 1, 2 and 5 effectively inhibited the growth of E-coli and Staphylococcus aureus. Conclusion: A combination of metabolomicand bioassay-guided protocol can efficiently predict the putative biologically active metabolites during the first stage of fractionation.

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New bioactive metabolites isolated from the endophytic fungus Stemphylium globuliferum isolated from Mentha pulegium growing in Morocco

Cited by 31 publications

References 0 publications

Elucidation of cladofulvin biosynthesis reveals a cytochrome P450 monooxygenase required for anthraquinone dimerization

Elucidation of cladofulvin biosynthesis reveals a cytochrome P450 monooxygenase required for anthraquinone dimerization

New Natural Product from Botryosphaeria australis, an Endophyte from Mangrove Avicennia marina

Metabolomics and Bioactivity Guided Isolation of Secondary Metabolites from the Endophytic Fungus Chaetomium sp.

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