Anti-<i>Cryptococcus</i> Phenalenones and Cyclic Tetrapeptides from <i>Auxarthron pseudauxarthron</i>

Li, Yan; Yue, Qiulin; Jayanetti, Dinith R.; Swenson, Dale C.; Bartholomeusz, Geoffrey; An, Zhiqiang; Gloer, James B.; Bills, Gerald F.

doi:10.1021/acs.jnatprod.7b00341

Cited by 17 publications

(18 citation statements)

References 33 publications

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“…The strategy to generate small-scale extracts from fungi for antifungal screening has been detailed previously (Li et al 2016, 2017). Briefly, each fungal strain from our collection was grown at a scale of 12 mL on a set of five media selected for their proven ability to stimulate production of secondary metabolites during 14 days.…”

Section: Methodsmentioning

confidence: 99%

Identification of cyclosporin C from Amphichorda felina using a Cryptococcus neoformans differential temperature sensitivity assay

Yan

Biggins³

et al. 2018

Appl Microbiol Biotechnol

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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.

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Section: Methodsmentioning

confidence: 99%

Identification of cyclosporin C from Amphichorda felina using a Cryptococcus neoformans differential temperature sensitivity assay

Yan

Biggins³

et al. 2018

Appl Microbiol Biotechnol

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“…Cyclic tetrapeptides auxarthrides A and B were obtained from cultures of the coprophilous fungus Auxarthron pseudauxarthron [ 97 ]. These compounds were inactive in the antifungal bioassay and against cancer cell lines.…”

Section: Recently Reported Naturally Occurring Bioactive Cyclopeptmentioning

confidence: 99%

Natural Cyclic Peptides as an Attractive Modality for Therapeutics: A Mini Review

2018

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Peptides are important biomolecules which facilitate the understanding of complex biological processes, which in turn could be serendipitous biological targets for future drugs. They are classified as a unique therapeutic niche and will play an important role as fascinating agents in the pharmaceutical landscape. Until now, more than 40 cyclic peptide drugs are currently in the market, and approximately one new cyclopeptide drug enters the market annually on average. Interestingly, the majority of clinically approved cyclic peptides are derived from natural sources, such as peptide antibiotics and human peptide hormones. In this report, the importance of cyclic peptides is discussed, and their role in drug discovery as interesting therapeutic biomolecules will be highlighted. Recently isolated naturally occurring cyclic peptides from microorganisms, sponges, and other sources with a wide range of pharmacological properties are reviewed herein.

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“…yielded an unprecedented epoxyacetal 4-(2,4,7-trioxa-bicyclo[4 .1.0]heptan-3-yl) phenol (65) with an MIC of 0.04 µg/mL against C. albicans strains and 1.3 µg/mL against the bacterium Micrococcus luteus [54]. Two phenalenones, auxarthrone A and D (66, 67) were obtained from fermentation extracts of an Auxarthron pseudauxarthron strain isolated from rabbit dung [55]. The compounds have MIC values of 3.2 and 6.4 µg/mL, respectively, against C. neoformans and C. albicans.…”

Section: Natural Product Antifungal Leads From Fungimentioning

confidence: 99%

A Decade of Antifungal Leads from Natural Products: 2010–2019

et al. 2019

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In this review, we discuss novel natural products discovered within the last decade that are reported to have antifungal activity against pathogenic species. Nearly a hundred natural products were identified that originate from bacteria, algae, fungi, sponges, and plants. Fungi were the most prolific source of antifungal compounds discovered during the period of review. The structural diversity of these antifungal leads encompasses all the major classes of natural products including polyketides, shikimate metabolites, terpenoids, alkaloids, and peptides.

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Anti-Cryptococcus Phenalenones and Cyclic Tetrapeptides from Auxarthron pseudauxarthron

Cited by 17 publications

References 33 publications

Identification of cyclosporin C from Amphichorda felina using a Cryptococcus neoformans differential temperature sensitivity assay

Identification of cyclosporin C from Amphichorda felina using a Cryptococcus neoformans differential temperature sensitivity assay

Natural Cyclic Peptides as an Attractive Modality for Therapeutics: A Mini Review

A Decade of Antifungal Leads from Natural Products: 2010–2019

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