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His efforts there reflected a burgeoning interest in fungal ecology, as he expanded his focus to other mycological groups, including coprophilous and carbonicolous fungi (Wicklow and Hirschfield [35]; Wicklow and Zak [40]). 36 Wicklow DT, Jordan AM, Gloer JB. 2009. LITERATURE CITED 1 Angawi RF, Swenson DC, Gloer JB, Wicklow DT. 2003. For those of us who were fortunate enough to know him, Don Wicklow will be fondly remembered as a good-humored, intellectually adventurous person, a model scientist and colleague who overflowed with ideas and boundless energy, and a genuine lover of all things mycological. [Extracted from the article]

Cryptococcus neoformans is a serious human pathogen with limited options for treatment. We have interrogated extracts from fungal fermentations to find Cryptococcus-inhibiting natural products using assays for growth inhibition and differential thermosensitivity. Extracts from fermentations of four fungal strains from wild and domestic animal dung from Arkansas and West Virginia, USA were identified as Preussia typharum. The extracts exhibited two antifungal regions. Purification of one region yielded new 24-carbon macrolides incorporating both a phosphoethanolamine unit and a bridging tetrahydrofuran ring. The structures of these metabolites were established mainly by analysis of high-resolution mass spectrometry and 2D NMR data. Relative configurations were assigned using NOESY data, and the structure assignments were supported by NMR comparison with similar compounds. These new metabolites are designated preussolides A and B. The second active region was caused by the cytotoxin, leptosin C. Genome sequencing of the four strains revealed biosynthetic gene clusters consistent with those known to encode phosphoethanolamine-bearing polyketide macrolides and the biosynthesis of dimeric epipolythiodioxopiperazines. All three compounds showed moderate to potent and selective antifungal activity toward the pathogenic yeast C. neoformans. [ABSTRACT FROM AUTHOR]

Strains of Eupenicillium crustaceum and related fungal species produce aflavinines and antiinsectan metabolites from the ascostromata. The antiinsectan activity of E. crustaceum NRRL 3332 generate the aflavinine analogs 10,23-dihydro-24,25-dehydroaflavinine and 10,23,24,25-tetrahydro-24- hydroxyaflavinine. E. reticulisporum NRRL 3446 produces 10,23-dihydro-24,25-dehydroaflavinine and pyripyropene while E. molle NRRL 13062 produces aflavinines and macrophorins.

Two antifungal metabolites stachybotrins A and B were obtained from ethyl acetate extracts of liquid cultures of Stachybotrys sp. (CS-710-1). Acetylation of stachybotrin A yielded a triacetate with two carbons bearing free OH groups as analyzed in 1H NMR spectrum. Stachybotrin B yielded a diacetate whose NMR data was almost similar to A. The differences between the two compounds were the absence of the vinylic CH2OH signal and the presence of a third methyl group singlet.

Silica gel column and reversed-phase high performance liquid chromatographies yield four new antiinsectan metabolites from the sclerotia of the fungus Aspergillus sulphureus. Sulpinines A-C and secopenitrem B belong to the paspaline/penitrem class of pesticide bases. Nuclear magnetic resonance studies and comparison with known penitrems establish the structures of the new antiinsectans. Sulpinine C has a unique ring system that includes an eight-membered-ring lactam. Sulphines A and B and secopenitrem B prove to be potent against the crop pest Helicoverpa zea.

Research was conducted to examine the isolation and characterization of antifungal metabolites yielded by Humicola fuscoatra which prevent the growth of Aspergillus flavus sclerotia. The mycoparasite Humicola fuscoatra Traaen NRRL 22980 was isolated from the sclerotium of A. flavus that was buried for three years in Georgia. Results indicate that H. fuscoatra generates various antifungal agents that are effective against A. flavus.

Gakolanone (3',5'-digeranyl-2',4',6',3-tetrahydroxybenzophenone; 1), a novel benzophenone derivative was isolated from the hexane extract of Garcinia kola Heckel stem-bark along with three known 3-8' linked biflavonoids: 3',4',4'',5,5',7,7'-heptahydroxy-3,8'-biflavanone (2); 3',4',5,5',5'',7,7'-heptahydroxy-4-methoxy-3,8'-biflavanone (3) and 4',4'',5,5',7,7'-hexahydroxy-3,8'-biflavanone (4) from the ethanol extract. The compounds were characterized primarily using 1 D and 2 D nuclear magnetic resonance spectroscopy and mass spectrometry and by comparing with literature. The compounds were subjected to in-vitro alpha-amylase enzyme inhibitory assay using DNSA (3,5-dinitrosalicylic acid) reagent with acarbose used as the standard drug. All the compounds were found to show alpha-amylase inhibitory activities with IC50 of 21.4 ± 1.5, 9.9 ± 0.2, 15.3 ± 2.3, 12.9 ± 2.3 µg/mL respectively. All the compounds exhibited better alpha-amylase inhibitory activities than the standard drug, acarbose (IC50= 38.1 ± 8.3 µg/mL). [ABSTRACT FROM AUTHOR]

The pentane extract of the sclerotia of Aspergillus nomium yields aspernomine, a cytotoxic antiinsectan fungal metabolite. The novel compond possesses a unique ring system and exhibits potent activity against the corn earworm Helicoverpa zea. The compound also exhibits cytotoxicity toward three human solid tumor cell lines. NMR spectroscopic studies at 600 MHz are conducted on aspernomine to determine its structure.

We used a temperature differential assay with the opportunistic fungal pathogen Cryptococcus neoformans as a simple screening platform to detect small molecules with antifungal activity in natural product extracts. By screening of a collection extracts from two different strains of the coprophilous fungus, Amphichorda felina, we detected strong, temperature-dependent antifungal activity using a two-plate agar zone of inhibition assay at 25 and 37 °C. Bioassay-guided fractionation of the crude extract followed by liquid chromatography–mass spectrometry (LC-MS) and nuclear magnetic resonance spectroscopy (NMR) identified cyclosporin C (CsC) as the main component of the crude extract responsible for growth inhibition of C. neoformans at 37 °C. The presence of CsC was confirmed by comparison with a commercial standard. We sequenced the genome of A. felina to identify and annotate the CsC biosynthetic gene cluster. The only previously characterized gene cluster for the biosynthesis of similar compounds is that of the related immunosuppressant drug cyclosporine A (CsA). The CsA and CsC gene clusters share a high degree of synteny and sequence similarity. Amino acid changes in the adenylation domain of the CsC nonribosomal peptide synthase’s sixth module may be responsible for the substitution of l-threonine compared to l-α-aminobutyric acid in the CsA peptide core. This screening strategy promises to yield additional antifungal natural products with a focused spectrum of antimicrobial activity. [ABSTRACT FROM AUTHOR]

Potent trienone and dienone steroid hormones undergo a coupled photohydration (in light)-thermal dehydration (in dark) cycle that ultimately increases their environmental persistence. Here, we studied the photolysis of dienogest, a dienone progestin prescribed as a next-generation oral contraceptive, and used high resolution mass spectrometry and both 1D and 2D nuclear magnetic resonance spectroscopy to identify its phototransformation products. Dienogest undergoes rapid direct photolysis (t1/2∼ 1–10 min), forming complex photoproduct mixtures across the pH range examined (pH 2 to 7). Identified products include three photohydrates that account for ∼80% of the converted mass at pH 7 and revert back to parent dienogest in the absence of light. Notably, we also identified two estrogenic compounds produced via the A-ring aromatization of dienogest, evidence for a photochemically-induced increase in estrogenic activity in product mixtures. These results imply that dienogest will undergo complete and facile photolytic transformation in sunlit surface water, yet exhibit greater environmental persistence than might be anticipated by inspection of kinetic rates. Photoproduct mixtures also include transformation products with different nuclear receptor binding capabilities than the parent compound dienogest. These outcomes reveal a dynamic fate and biological risk profile for dienogest that must also take into account the composition and endocrine activity of its transformation products. Collectively, this study further illustrates the need for more holistic regulatory, risk assessment, and monitoring approaches for high potency synthetic pharmaceuticals and their bioactive transformation products. [ABSTRACT FROM AUTHOR]

Petriellin A was obtained from an EtOAc extract of the Petriella sordida culture and crystallized from CHCl3-acetone. The resulting compound is an antifungal cyclic dipsipeptide having an IC(sub 50) value of 10 microgram/mL. Petriellin A is ninhydrin negative revealing a N-terminus blockage or a cyclic peptide and the spin systems are in accordance with the presence of beta-phenyllactic acid and 12 amino acid residues. It exhibits potent antifungal activity against successional Ascobolus furfaraceus and Sordaria fimicola, both fungi.

Background: Increased atmospheric carbon dioxide (CO2) levels predicted to occur before the end of the century will impact plant metabolism. In addition, nitrate availability will affect metabolism and levels of nitrogen-containing defense compounds, such as glucosinolates (GSLs). We compared Arabidopsis foliar metabolic profile in plants grown under two CO2 regimes (440 vs 880 ppm), nitrate fertilization (1 mM vs 10 mM) and in response to mechanical damage of rosette leaves. Results: Constitutive foliar metabolites in nitrate-limited plants show distinct global patterns depending on atmospheric CO2 levels; in contrast, plants grown under higher nitrate fertilization under elevated atmospheric CO2 conditions have a unique metabolite signature. Nitrate fertilization dampens the jasmonate burst in response to wounding in plants grown at elevated CO2 levels. Leaf GSL profile mirrors the jasmonate burst; in particular, indole GSLs increase in response to damage in plants grown at ambient CO2 but only in nitrate-limited plants grown under elevated CO2 conditions. Conclusions: This may reflect a reduced capacity of C3 plants grown under enriched CO2 and nitrate levels to signal changes in oxidative stress and has implications for future agricultural management practices. [ABSTRACT FROM AUTHOR]

Chemical investigations of two fungal isolates initially identified as members of the genusPhialemoniumare described. Both isolates were obtained as colonists of other fungi collected on the island of Hawaii and were later assigned asP. curvatum. However,P. curvatumhas recently been reclassified as a member of a new genus (Phialemoniopsis) and renamed asPhialemoniopsis curvata. Studies of solid–substrate fermentation cultures of one of these isolates afforded an oxirapentyn analogue and destruxin A4as major components, while analysis of the second strain led to the isolation of several simple aromatic metabolites and a compound of mixed biogenetic origin called gabusectin that had previously been reported only in a patent. Structures were assigned mainly by detailed nuclear magnetic resonance and mass spectrometry analysis, and those of two of the major components were confirmed by X-ray crystallography. This report constitutes the first description of secondary metabolites from a member of the genusPhialemoniopsis. [ABSTRACT FROM AUTHOR]

Highlights: [•] Coprophilous fungi can serve as model systems for elucidating ecological functions of antibiotics. [•] Understanding their chemical interactions and defenses could lead to novel approaches for development of antibiotics. [•] Post-genomic methods enable experimental manipulation of this convenient model community in ways previously unimaginable. [•] Emerging technologies offer multiple entry points to rationally excavate beneath the fungal chemical phenotype and unravel how and why antibiotics are made. [•] We argue strongly that coprophilous fungi will be a productive reservoir of antibiotics and other bioactive metabolites. [Copyright &y& Elsevier]

The article offers information on the halogenated organic molecules of Rhodomelaceae origin, a marine red algal family. It states that halogen-containing organic molecules from the Rhodomelaceae represent unique secondary metabolites. It discusses the structures, occurrence and synthesis of several halogenated organic molecules including sesquiterpenes, polyethers and indoles. It highlights the chemotaxonomic significance of organic halogenated compounds.

A new aliphatic acid named japodic acid (1) with a gem-dimethyl cyclopropane ring has been isolated from the roots of Jatropha podagrica. Its structure was established by 1D and 2D NMR and mass spectrometric data. Two other known compounds, erythrinasinate (2) and fraxidin (3) were also isolated from this plant for the first time. Japodic acid showed mild insect growth inhibition activity against Helicoverpa zea (37% growth reduction at 100 ppm). Fraxidin and erythrinasinate exhibited antibacterial activity against Bacillus subtilis while japodic acid was inactive in the antibacterial assays conducted. [ABSTRACT FROM AUTHOR]

Sphaerostilbella toxica is a mycoparasitic fungus that can be found parasitizing wood-decay basidiomycetes in the southern USA. Organic solvent extracts of fermented strains of S. toxica exhibited potent antimicrobial activity, including potent growth inhibition of human pathogenic yeasts Candida albicans and Cryptococcus neoformans, the respiratory pathogenic fungus Aspergillus fumigatus, and the Gram-positive bacterium Staphylococcus aureus. Bioassay-guided separations led to the purification and structure elucidation of new peptaibiotics designated as sphaerostilbellins A and B. Their structures were established mainly by analysis of NMR and HRMS data, verification of amino acid composition by Marfey's method, and by comparison with published data of known compounds. They incorporate intriguing structural features, including an N-terminal 2-methyl-3-oxo-tetradecanoyl (MOTDA) residue and a C-terminal putrescine residue. The minimal inhibitory concentrations for sphaerostilbellins A and B were measured as 2 μM each for C. neoformans, 1 μM each for A. fumigatus, and 4 and 2 μM, respectively, for C. albicans. Murine macrophage cells were unaffected at these concentrations. [ABSTRACT FROM AUTHOR]