title: Sensitivity of Neurospora crassa to a marine-derived Aspergillus tubingensis anhydride exhibiting antifungal activity that is mediated by the MAS1 protein.
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 ∆mas-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 ∆mas-1 strain, suggesting the gene product is involved in cell wall biosynthesis and the novel anhydride interferes with its function.
authors.affiliation: Department of Plant Pathology and Microbiology, The R.H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot 76100, Israel. liat.koch@mail.huji.ac.il.
authors.forename: Liat
authors.initials: L
authors.lastname: Koch
authors.affiliation: School of Chemistry, Raymond and Beverly Sackler Faculty of Exact Sciences, Tel Aviv 69978, Israel. anatlodin@gmail.com.
authors.forename: Anat
authors.initials: A
authors.lastname: Lodin
authors.affiliation: Department of Plant Pathology and Microbiology, The R.H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot 76100, Israel. inbiherold@gmail.com.
authors.forename: Inbal
authors.initials: I
authors.lastname: Herold
authors.affiliation: Department of Zoology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel. Milan@post.tau.ac.il.
authors.forename: Micha
authors.initials: M
authors.lastname: Ilan
authors.affiliation: School of Chemistry, Raymond and Beverly Sackler Faculty of Exact Sciences, Tel Aviv 69978, Israel. carmeli@post.tau.ac.il.
authors.forename: Shmuel
authors.initials: S
authors.lastname: Carmeli
authors.affiliation: Department of Plant Pathology and Microbiology, The R.H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot 76100, Israel. Oded.Yarden@mail.huji.ac.il.
authors.forename: Oded
authors.initials: O
authors.lastname: Yarden
mesh_terms: D000812:Anhydrides / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D000935:Antifungal Agents / Q000302:isolation & purification / Q000494:pharmacology*; D001230:Aspergillus / Q000737:chemistry* / Q000235:genetics; D002473:Cell Wall / Q000187:drug effects; D002687:Chitin Synthase / Q000096:biosynthesis / Q000235:genetics; D009492:Neurospora crassa / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D011161:Porifera / Q000382:microbiology; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000737:chemistry* / Q000235:genetics*; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry* / Q000235:genetics*
chemical_list: D000812:Anhydrides; D000935:Antifungal Agents; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D043562:Receptors, G-Protein-Coupled; D002687:Chitin Synthase