Sheptide A: an antimalarial cyclic pentapeptide from a fungal strain in the Herpotrichiellaceae.

As part of ongoing efforts to isolate biologically active fungal metabolites, a cyclic pentapeptide, sheptide A (1), was discovered from strain MSX53339 (Herpotrichiellaceae). The structure and sequence of 1 were determined primarily by analysis of 2D NMR and HRMS/MS data, while the absolute configuration was assigned using a modified version of Marfey's method. In an in vitro assay for antimalarial potency, 1 displayed a pEC value of 5.

New tricks for old dogs: Two new macrocyclic trichothecene epimers and absolute configuration of 16-hydroxyverrucarin B.

Two new compounds, 3'-epi-16-hydroxyverrucarin A and 3'-epiverrucarin X, have been isolated and identified, and the characterization data of a series of known trichothecenes have been refined. The interesting structure and potent biological activities of macrocyclic trichothecenes have been of interest to the scientific community for several decades. However, some of the characterization data for the older analogues of this class are not well documented, either because of a lack of absolute configuration or a lack of clarity in the NMR data, largely due to technological limitations at the time they were discovered.

Media studies to enhance the production of verticillins facilitated by in situ chemical analysis.

Verticillins are a group of epipolythiodioxopiperazine alkaloids that have displayed potent cytotoxicity. To evaluate their potential further, a larger supply of these compounds was needed for both in vivo studies and analogue development via semisynthesis. To optimize the biosynthesis of these secondary metabolites, their production was analyzed in two different fungal strains (MSX59553 and MSX79542) under a suite of fermentation conditions.

Optimizing production and evaluating biosynthesis in situ of a herbicidal compound, mevalocidin, from Coniolariella sp.

Mevalocidin is a fungal secondary metabolite produced by Coniolariella sp. It is a unique phytotoxin that demonstrates broad spectrum post-emergent herbicidal properties. With limited options for weed control, the commercialization of a natural product pesticide would be beneficial to organic farming.

Epigenetic Manipulation of a Filamentous Fungus by the Proteasome-Inhibitor Bortezomib Induces the Production of an Additional Secondary Metabolite.

The use of epigenetic modifiers, such as histone deacetylase inhibitors and DNA methyltransferase inhibitors, has been explored increasingly as a technique to induce the production of additional microbial secondary metabolites. The application of such molecules to microbial cultures has been shown to upregulate otherwise suppressed genes, and in several cases has led to the production of new molecular structures. In this study, the proteasome inhibitor bortezomib was used to induce the production of an additional metabolite from a filamentous fungus (Pleosporales).

Cytotoxic epipolythiodioxopiperazine alkaloids from filamentous fungi of the Bionectriaceae.

Bioactivity-directed fractionation of the organic extracts of two filamentous fungi of the Bionectriaceae, strains MSX 64546 and MSX 59553 from the Mycosynthetix library, led to the isolation of a new dimeric epipolythiodioxopiperazine alkaloid, verticillin H (1), along with six related analogs, Sch 52900 (2), verticillin A (3), gliocladicillin C (4), Sch 52901 (5), 11'-deoxyverticillin A (6) and gliocladicillin A (7). The structures of compounds 1-7 were determined by extensive NMR and HRMS analyses, as well as by comparisons to the literature. All compounds (1-7) were evaluated for cytotoxicity against a panel of human cancer cell lines, displaying IC(50) values ranging from 1.

Cytotoxic xanthone-anthraquinone heterodimers from an unidentified fungus of the order Hypocreales (MSX 17022).

Two new xanthone-anthraquinone heterodimers, acremoxanthone C (5) and acremoxanthone D (2), have been isolated from an extract of an unidentified fungus of the order Hypocreales (MSX 17022) by bioactivity-directed fractionation as part of a search for anticancer leads from filamentous fungi. Two known related compounds, acremonidin A (4) and acremonidin C (3) were also isolated, as was a known benzophenone, moniliphenone (1). The structures of these isolates were determined via extensive use of spectroscopic and spectrometric tools in conjunction with comparisons to the literature.

Obionin B: An o-pyranonaphthoquinone decaketide from an unidentified fungus (MSX 63619) from the Order Pleosporales.

A fungal extract (MSX 63619), from the Mycosynthetix library of over 50,000 fungi, displayed promising cytotoxicity against a human tumor cell panel. Bioactivity-directed fractionation led to the isolation of an o-pyranonaphthoquinone decaketide, which we termed obionin B (1). The structure of 1 was deduced via spectroscopic and spectrometric techniques.

Global nutritional profiling for mutant and chemical mode-of-action analysis in filamentous fungi.

We describe a method for gene function discovery and chemical mode-of-action analysis via nutrient utilization using a high throughput Nutritional Profiling platform suitable for filamentous microorganisms. We have optimized the growth conditions for each fungal species to produce reproducible optical density growth measurements in microtiter plates. We validated the Nutritional Profiling platform using a nitrogen source utilization assay to analyze 21 Aspergillus nidulans strains with mutations in the master nitrogen regulatory gene, areA.