Eight new potentiators of antifungal amphotericin B (AmB) activity, phialotides A to H, were isolated from the fermentation broths of the rare fungus Pseudophialophora sp. BF-0158. The structures of phialotides were elucidated by spectroscopic analyses, including NMR and MS, and degradation studies. Phialotides were novel polyketide glycosides consisting of a 1,3-dimethylbut-1-ene (C6-unit) repeating substructure and one to three hexopyranoses. None of the phialotides exhibited antifungal activity, whereas all potentiated AmB activity against several fungi. Phialotide F was the most effective potentiator of AmB activity against Candida albicans, with a decrease in the MIC from 0.50 to 0.016 µg ml−1 being observed in combination with phialotide F at 1.0 µg ml−1.
This is a preview of subscription content, access via your institution
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Rent or buy this article
Get just this article for as long as you need it
Prices may be subject to local taxes which are calculated during checkout
Trejo WH, Bennett RE. Streptomyces nodosus sp. n., the amphotericin-producing organism. J Bacteriol. 1963;85:436–9.
Aversa F, Busca A, Candoni A, Cesaro S, Girmenia C, Luppi M, et al. Liposomal amphotericin B (AmBisome®) at beginning of its third decade of clinical use. J Chemother. 2017;29:131–43.
Stone NR, Bicanic T, Salim R, Hope W. Liposomal amphotericin B (AmBisome(®)): a review of the pharmacokinetics, pharmacodynamics, clinical experience and future directions. Drugs. 2016;76:485–500.
Uchida R, Kondo A, Yagi A, Nonaka K, Masuma R, Kobayashi K, et al. Simpotentin, a new potentiator of amphotericin B activity against Candida albicans, produced by Simplicillium minatense FKI-4981. J Antibiot. 2019;72:134–40.
Fukuda T, Nagai K, Yagi A, Kobayashi K, Uchida R, Yasuhara T, et al. Nectriatide, a potentiator of amphotericin B activity from Nectriaceae sp. BF-0114. J Nat Prod. 2019;82:2673–81.
Bock K, Lundt I, Pedersen C. Assignment of anomer structure to carbohydrates through geminal 13C-1H coupling constants. Tetrahedron Lett. 1973;13:1037–40.
Kohno J, Nishio M, Sakurai M, Kawano K, Hiramatsu H, Kameda N, et al. Isolation and structure determination of TMC-151s: Novel polyketide antibiotics from Gliocladium catenulatum Gilman & Abbott TC 1280. Tetrahedron 1999;55:7771–86.
Tanaka T, Nakashima T, Ueda T, Tomii K, Kouno I. Facile discrimination of aldose enantiomers by reversed-phase HPLC. Chem Pharm Bull. 2007;55:899–901.
Clinical and Laboratory Standards Institute (CLSI). Reference method for broth dilution antifungal susceptibility testing of yeasts. 3rd ed. CLSI document M27-A3. Wayne, PA: Clinical and Laboratory Standards Institute; 2008.
Clinical and Laboratory Standards Institute (CLSI): Reference method for broth dilution antifungal susceptibility testing of filamentous fungi; approved standard CLSI document M38-A2. 3rd ed. Wayne, PA: Clinical and Laboratory Standards Institute; 2008.
Luo J, Walsh E, Blystone D, Zhang N. Five new Pseudophialophora species from grass roots in the oligotrophic pine barrens ecosystem. Fungal Biol. 2015;119:1205–15.
Wang B, You, King JB, Cai S, Park E, Powell DR, et al. Polyketide glycosides from Bionectria ochroleuca inhibit Candida albicans biofilm formation. J Nat Prod. 2014;77:2273–9.
Kasai Y, Komatsu K, Shigemori H, Tsuda M, Mikami Y, Kobayashi J. Cladionol A, a polyketide glycoside from marine-derived fungus Gliocladium species. J Nat Prod. 2005;68:777–9.
Kohno J, Asai Y, Nishio M, Sakurai M, Kawano K, Hiramatsu H, et al. Komatsubara S. TMC-171A, B, C and TMC-154, novel polyketide antibiotics produced by Gliocladium sp. TC 1304 and TC 1282. J Antibiot. 1999;52:1114–23.
Kumazawa S, Kanda M, Utagawa M, Chiba N, Ohtani H, Mikawa T. MK7924, a novel metabolite with nematocidal activity from Coronophora gregaria. J Antibiot. 2003;56:652–4.
Tomoda H, Ohyama Y, Abe T, Tabata N, Namikoshi M, Yamaguchi Y, et al. Roselipins, inhibitors of diacylglycerol acyltransferase, produced by Gliocladium roseum KF-1040. J Antibiot. 1999;52:689–94.
Tabata N, Ohyama Y, Tomoda H, Abe T, Namikoshi M, Ōmura S. Structure elucidation of roselipins, inhibitors of diacylglycerol acyltransferase produced by Gliocladium roseum KF-1040. J Antibiot. 1999;52:815–26.
Ishijima H, Uchida R, Ohtawa M, Kondo A, Nagai K, Shima K, et al. Simplifungin and valsafungins, antifungal antibiotics of fungal origin. J Org Chem. 2016;81:7373–83.
We express our thanks to Dr. Kenichiro Nagai and Ms. Noriko Sato of the School of Pharmacy, Kitasato University for measurements of NMR and mass spectra. This work was supported by JSPS KAKENHI Grant Numbers 16H05095 (to RU) and 21310146 (to HT).
Conflict of interest
The authors declare that they have no conflict of interest.
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Polyketide glycosides phialotides A to H, new potentiators of amphotericin B activity, produced by <i>Pseudophialophora</i> sp. BF-0158
Rights and permissions
About this article
Cite this article
Yagi, A., Uchida, R., Kobayashi, K. et al. Polyketide glycosides phialotides A to H, new potentiators of amphotericin B activity, produced by Pseudophialophora sp. BF-0158. J Antibiot 73, 211–223 (2020). https://doi.org/10.1038/s41429-019-0276-7
This article is cited by
New piericidin rhamnosides as potentiators of amphotericin B activity against Candida albicans produced by actinomycete strain TMPU-A0287
The Journal of Antibiotics (2023)
Indispensable role of microbes in anticancer drugs and discovery trends
Applied Microbiology and Biotechnology (2022)
Podogigants A and B, two new potentiators of amphotericin B activity, from Sordariomycete Podostroma giganteum
Journal of Natural Medicines (2021)