The proteomics data of Aspergillus niger ATCC 1015 after spirolactone treatment

ABSTRACT: Fungal infections pose a great threat to public health and the existing four classes of antifungals have limitations due to high toxicity, drug-drug interactions, and emerging drug-resistance. Streptomyces spp. represent an important source of antimicrobial substances, notably including the antifungal agent amphotericin B. The rapamycin-producer Streptomyces iranensis displayed strong antifungal activities against Aspergillus. Revisiting its genome revealed several intriguing biosynthetic gene clusters, including one unparalleled Type I polyketide synthase, which codes for uncharacterized metabolites. The identification of a novel macrolide spirolactone was facilitated through CRISPR-based gene editing, HR-ESI-MS analysis, followed by fermentation and purification processes. Their structures and absolute configurations were confirmed by NMR, MS and X-ray crystallography. Spirolactone A harbors an undescribed carbon skeleton with 13 chiral centers, featuring a rare ?-lactone moiety, a [6,6]-spiroketal ring, and an unprecedented 7-oxo-octylmalonyl-CoA extender unit. Spirolactone displayed profound antifungal effects against numerous fungal pathogens, e.g. the genus Talaromyces and several sections of Aspergillus including clinically relevant species such as Aspergillus niger and A. tubingensis (section Nigri), A. terreus (section Terrei) and the azol-resistant A. calidoustus (section Usti). Proteomics analysis revealed spirolactone potentially disrupted the integrity of fungal cell walls and induced the expression of stress-response proteins in A. niger. Spirolactone A represents a new class of potential agents leading to combat fungal infections.

INSTRUMENT(S): LTQ Orbitrap Discovery

ORGANISM(S): Aspergillus Niger Atcc 1015 (ncbitaxon:380704)

SUBMITTER: Ling Ding  

PROVIDER: MSV000094235 | MassIVE | Tue Mar 05 00:01:00 GMT 2024

REPOSITORIES: MassIVE