Isolation, Structure Elucidation, and Biological Activity of Virgineone from <i>Lachnum virgineum</i> Using the Genome-Wide <i>Candida albicans</i> Fitness Test

Ondeyka, John G.; Harris, Guy H.; Zink, Deborah L.; Basilio, Ángela; Vicente, Francisca; Bills, Gerald F.; Platas, Gonzalo; Collado, Javier; González, Antonio; Cruz, Mercedes de la; Martín, Jesús; Kahn, Jennifer Nielsen; Galuska, Stefan; Giacobbe, Robert A.; Abruzzo, George K.; Hickey, Emily; Liberator, Paul; Jiang, Bo; Xu, Deming; Roemer, Terry; Singh, Sheo B.

doi:10.1021/np800511r

Cited by 48 publications

(53 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Applying this approach, MOA (mechanism of action) determination has been successfully validated with known bioactive compounds whose MOA is well characterized and extended to elucidating MOA of antifungal synthetic compounds and purified natural products (Roemer et al 2003, Rodriguez-Suarez et al 2007, Ondeyka et al 2009. CaFT recently was applied to crude natural products extracts and incorporated into our antifungal discovery platform.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Discovery of the parnafungins, antifungal metabolites that inhibit mRNA polyadenylation, from theFusarium larvarumcomplex and other Hypocrealean fungi

Bills

Platas²,

Overy³

et al. 2009

Mycologia

Self Cite

View full text Add to dashboard Cite

Evaluation of fungal fermentation extracts with whole cell Candida albicans activity resulted in the identification of a novel class of isoxazolidinone-containing metabolites named parnafungins. Chemical-genetic profiling with the C. albicans fitness test identified the biochemical target as inhibition of polyadenosine polymerase, a component of the mRNA cleavage and polyadenylation complex. Parnafungins were discovered from fermentation extracts of fungi resembling F. larvarum isolated from plants, plant litter and lichens. Furthermore authentic strains of F. larvarum var. larvarum and F. larvarum var. rubrum could be induced to produce parnafungins and their degradation products in low titers. Relationships among strains of the F. larvarum complex (FLC), including parnafungin-producing strains, were examined by cladistic analyses of rDNA, mitochondrial rDNA, and two protein-coding genes, comparisons of antifungal activity and antifungal metabolite profiles, and morphological phenotypes. Integrated analyses of these data led to the conclusion that the diversity within the FLC exceeded the one-to-one correspondence between F. larvarum and its teleomorph Cosmospora aurantiicola. Based on multiple gene sequence analyses, strains of the FLC formed a monophyletic clade inclusive of the parnafungin-producing strains. The FLC, including newly discovered parnafungin-producing strains, could be resolved into at least six different lineages, possibly representing cryptic' species, of which one was not fully resolved from F. larvarum var. rubrum. Fusarium larvarum var. rubrum represents a species distinct from var. larvarum. Finally we report that two other species from the Hypocreales, Trichonectria rectipila and Cladobotryum pinarense, are able to produce parnafungins and their open-ring forms.

show abstract

Section: Introductionmentioning

confidence: 99%

“…All subsequent strain comparisons employed medium MMK2 in both 40 mL EPA vials and 24-well fermentation plates. Procedures for growing liquid inoculum and inoculating fermentations have been described by Bills et al (2008) and Ondeyka et al (2009).…”

Section: Introductionmentioning

confidence: 99%

Discovery of the parnafungins, antifungal metabolites that inhibit mRNA polyadenylation, from theFusarium larvarumcomplex and other Hypocrealean fungi

Bills

Platas²,

Overy³

et al. 2009

Mycologia

Self Cite

View full text Add to dashboard Cite

show abstract

“…The 28S rDNA fragments, containing D1−D2 and ITS regions, were PCR amplified, and sequence alignments 12 and phylogenetic analyses were performed as previously described. 13 In culture, the fungus produced pale pink to peach-colored aerial mycelium ( Figure S10A). Simple to sparsely branched phialides arose from the agar surface and aerial hyphae ( Figure S10B−D).…”

Section: ■ Experimental Sectionmentioning

confidence: 99%

Lasionectrin, a Naphthopyrone from a Lasionectria sp.

et al. 2012

Self Cite

View full text Add to dashboard Cite

A new naphthopyrone derivative, lasionectrin (1), was isolated from fermentations of an Acremonium-like fungus provisionally identified as a Lasionectria sp. (Ascomycota, Hypocreales) and isolated from forest leaf litter from Equatorial Guinea. Its structure was determined by a combination of spectroscopic techniques, including UV, (+)-HRESIMS, and 1D and 2D NMR spectroscopy, and comparison with published data for related fungal metabolites. Compound 1 inhibited the growth of Plasmodium falciparum with an IC(50) value of 11 μM.

show abstract

“…[51][52][53][54] 11.4 Discovery of New Antibacterial Compounds 11.4.1 Antibacterial Compounds Derived from the Target-based Antisense-Sensitized S. aureus Screening…”

Section: Novel Approaches To Exploit Natural Products From Microbial mentioning

confidence: 99%

Chapter 11. Novel Approaches to Exploit Natural Products from Microbial Resources

Genilloud¹,

Vicente²

2012

Drug Discovery

View full text Add to dashboard Cite

Isolation, Structure Elucidation, and Biological Activity of Virgineone from Lachnum virgineum Using the Genome-Wide Candida albicans Fitness Test

Cited by 48 publications

References 22 publications

Discovery of the parnafungins, antifungal metabolites that inhibit mRNA polyadenylation, from theFusarium larvarumcomplex and other Hypocrealean fungi

Discovery of the parnafungins, antifungal metabolites that inhibit mRNA polyadenylation, from theFusarium larvarumcomplex and other Hypocrealean fungi

Lasionectrin, a Naphthopyrone from a Lasionectria sp.

Chapter 11. Novel Approaches to Exploit Natural Products from Microbial Resources

Contact Info

Product

Resources

About