Sensitivity of Neurospora crassa to a marine-derived Aspergillus tubingensis anhydride exhibiting antifungal activity that is mediated by the MAS1 protein

Liat Koch, Anat Lodin, Inbal Herold, Micha Ilan, Shmuel Carmeli, Oded Yarden*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

The fungus Aspergillus tubingensis (strain OY907) was isolated from the Mediterranean marine sponge Ircinia variabilis. Extracellular extracts produced by this strain were found to inhibit the growth of several fungi. Among the secreted extract components, a novel anhydride metabolite, tubingenoic anhydride A (1) as well as the known 2-carboxymethyl-3-hexylmaleic acid anhydride, asperic acid, and campyrone A and C were purified and their structure elucidated. Compound 1 and 2-carboxymethyl-3-hexylmaleic acid anhydride inhibited Neurospora crassa growth (MIC = 330 and 207 μM, respectively) and affected hyphal morphology. We produced a N. crassa mutant exhibiting tolerance to 1 and found that a yet-uncharacterized gene, designated mas-1, whose product is a cytosolic protein, confers sensitivity to this compound. The Δmas-1 strain showed increased tolerance to sublethal concentrations of the chitin synthase inhibitor polyoxin D, when compared to the wild type. In addition, the expression of chitin synthase genes was highly elevated in the Δmas-1 strain, suggesting the gene product is involved in cell wall biosynthesis and the novel anhydride interferes with its function.

Original languageEnglish
Pages (from-to)4713-4731
Number of pages19
JournalMarine Drugs
Volume12
Issue number9
DOIs
StatePublished - 1 Sep 2014

Bibliographical note

Publisher Copyright:
© 2014 by the authors; licensee MDPI.

Keywords

  • Antifungal
  • Aspergillus tubingensis
  • Cell wall
  • Chitin synthase
  • Natural products
  • Neurospora crassa

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