Chrysosporide, a Cyclic Pentapeptide from a New Zealand Sample of the Fungus <i>Sepedonium </i><i>chrysospermum</i>

The application of an HPLC bioactivity profiling/microtiter plate technique in conjunction with microprobe NMR instrumentation and access to the AntiMarin database has led to the isolation of a new 1. In this example, 1 was isolated from a cytotoxic fraction of an extract obtained from marine-derived Streptomyces sp. cultured on Starch Casein Agar (SCA) medium. The 1D and 2D 1H NMR and ESIMS data obtained from 20 μg of compound 1 fully defined the structure. The known 2 was also isolated and readily dereplicated using this approach.

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“…Solvents used for extraction and isolation were distilled prior to use. Bioactivity assays were made using standard protocols [16, 17]. …”

Section: Methodsmentioning

confidence: 99%

“…A daughter plate was prepared by transferring an aliquot (5 μ L) from each well of the master plate. After complete evaporation of the solvent, the wells in the daughter plate were analyzed for activity against P388 murine leukemia cells as described previously [16, 17]. …”

Section: Methodsmentioning

confidence: 99%

The Isolation of a NewS-Methyl Benzothioate Compound from a Marine-DerivedStreptomycessp.

Mahyudin

Blunt

Cole

et al. 2012

Journal of Biomedicine and Biotechnology

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“…DHMBA was first isolated as a side product from the New Zealand fungus Sepedonium chrysospermum in 2006 (43) and was recently discovered in Aspergillus nidulans (1). Until 2006, it was known only as an intermediate in the chemical synthesis of azaphilones (63).…”

Section: Discussionmentioning

confidence: 99%

Breaking the Silence: Protein Stabilization Uncovers Silenced Biosynthetic Gene Clusters in the Fungus Aspergillus nidulans

Gerke

Bayram

Feussner

et al. 2012

Appl Environ Microbiol

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The genomes of filamentous fungi comprise numerous putative gene clusters coding for the biosynthesis of chemically and structurally diverse secondary metabolites (SMs), which are rarely expressed under laboratory conditions. Previous approaches to activate these genes were based primarily on artificially targeting the cellular protein synthesis apparatus. Here, we applied an alternative approach of genetically impairing the protein degradation apparatus of the model fungus Aspergillus nidulans by deleting the conserved eukaryotic csnE/CSN5 deneddylase subunit of the COP9 signalosome. This defect in protein degradation results in the activation of a previously silenced gene cluster comprising a polyketide synthase gene producing the antibiotic 2,4-dihydroxy-3-methyl-6-(2-oxopropyl)benzaldehyde (DHMBA). The csnE/CSN5 gene is highly conserved in fungi, and therefore, the deletion is a feasible approach for the identification of new SMs. Since its discovery by Fleming in the 1920s, fungal penicillin has saved the lives of millions. Currently, the World Health Organization forecasts that the dramatic increase in antimicrobial resistance all over the world might lead to a disaster and proclaims a need for novel drugs (22). Certain fungi, plants, and bacteria produce various potent secondary metabolites (SMs) that span a wide field of structurally and chemically diverse natural products. With almost 1.5 million species (33), the fungal kingdom is a major reservoir for bioactive natural products as beneficial antibiotics and antitumor drugs but also as deleterious mycotoxins and food contaminants (28,38). Although many fungal SMs have been described and tested, their complete potential is by far not exploited.In recent years, different approaches were applied to find novel bioactive SMs either in new species or in already established model organisms. New geographical spots exhibiting extreme conditions were explored in order to find new species producing as-yet-unknown natural products (37). An alternative approach is the exploration of the full genomic potential of already known species by genomic mining (13,14,30,76). Genomic sequencing revealed that there are many more genes for the biosynthesis of SMs than the metabolites already identified. These genes are often clustered, but most of them are rarely expressed under laboratory conditions (35), making the identification of their chemical products challenging. Two major strategies were applied to activate hidden genes: (i) changing the environment or (ii) genetic engineering (19,35,56). (i) The OSMAC (one strain, many compounds) approach activates silent gene clusters by cultivating microorganisms under different conditions (10, 75). Alternatively, physical contact with an opponent results in the uncovering of hidden clusters by activating defense mechanisms (58). (ii) Genetic engineering is focused primarily on expressing complete gene clusters in heterologous hosts (53, 77) or on altering the cellular transcription or protein synthesis machinery. Thus, SM synthesi...

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“…Fr. include the polyketide sepedonin and its derivatives (Wright et al 1970;Nagao et al 2006), the antifungal compound chrysodin (Closse and Hauser 1973), the family of chrysospermins, 19-membered peptaibols with antibacterial and antifungal activities (Dornberger et al 1995), the cyclic pentapeptide chrysosporide (Mitova et al 2006), and the peptaibol antibiotic, chrysaibol (Mitova et al 2008).…”

Section: Introductionmentioning

confidence: 99%

A hemolytic peptide from the mycophilic fungus Sepedonium chrysospermum (Bull.) Fr.

Sanguineti

Cosulich

Salis

et al. 2011

Appl Microbiol Biotechnol

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The hemolytic activity of an extract of the mycoparasite Sepedonium chrysospermum (teleomorph Hypomyces chrysospermus) was detected and characterized. Extraction of the fungal biomass by methanol yielded a fraction in which the hemolytic activity against human red blood cells corresponded to a peptide with a molecular mass of 7,653.72 Da and an isoelectric point of approximately 5.8. The peptide was temperature resistant, and the hemolysis was only partially inhibited, even after a 30-min pre-incubation at 100°C. Its hemolytic activity was unaffected by treatment with proteolytic enzymes such as trypsin. Among the divalent cations assayed, Hg(2+) was the strongest inhibitor of hemolysis. The reducing agent, dithiothreitol, and the membrane lipid, cholesterol, demonstrated concentration-dependent inhibitory activities. Finally, hemolytic activity triggered by the peptide was analyzed by scanning electron microscopy, and a pore-forming activity was detected.

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Chrysosporide, a Cyclic Pentapeptide from a New Zealand Sample of the Fungus Sepedonium chrysospermum

Cited by 20 publications

References 20 publications

The Isolation of a NewS-Methyl Benzothioate Compound from a Marine-DerivedStreptomycessp.

The Isolation of a NewS-Methyl Benzothioate Compound from a Marine-DerivedStreptomycessp.

Breaking the Silence: Protein Stabilization Uncovers Silenced Biosynthetic Gene Clusters in the Fungus Aspergillus nidulans

A hemolytic peptide from the mycophilic fungus Sepedonium chrysospermum (Bull.) Fr.

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