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.

Biosynthesis of alkylcitric acids inAspergillus nigerinvolves both co-localized and unlinked genes

“…Alkylcitrates isolated from filamentous fungi include the tensyuic acids (A-F) [22][23] , hexylaconitic acid anhydride [23][24] , hexylitaconic acid [24][25] , hexylcitric acid 26 and hydroxylated hexylitaconic acids 27 (Figure 1). Members of alkylcitric acids have been shown to possess useful bioactive properties including plant root growth promotion (hexylitaconic acid) 24 , anti-fungal (hexylaconitic acid anhydride) 28 , antibiotic, and anti-parasitic properties (tensyuic acid C) 22 . The production level of these bioactive alkylcitrates under laboratory conditions is low (ng-mg/L range) 22,24,[26][27] .…”

Beyond the biosynthetic gene cluster paradigm: Genome-wide co-expression networks connect clustered and unclustered transcription factors to secondary metabolic pathways

“…In parallel to this study, BGC 34 ( Figure 3 ) was recently demonstrated to be responsible for alkyl citrate production in A. niger NRRL3 38 . For this SM class, a range of bioactivities has been reported, including antiparasitic 48 , antifungal 49 antibacterial 50 , and plant root growth promotion effects 51 . Other complex alkyl citrates (zaragozic acids, also called squalestatins) have been shown to be amongst the most potent natural squalene synthase inhibitors 52,53 .…”

Altering Neurospora crassa MOB2A exposes its functions in development and affects its interaction with the NDR kinase COT1

“…C). Such occurrences have also been observed in the case of inactivation of the second N. crassa NDR kinase, dbf‐2 (NCU09071.7; Dvash et al ., ), as well as when the mas‐1 gene (NCU03140.7; shown to be involved in cell wall integrity) had been deleted (Koch et al ., ). One explanation for the leakage phenomenon may be the occurrence of a defect in aerial hyphae quality, such as imposed by a flaw in cell wall integrity.…”