Identification of Secondary Metabolites from Aspergillus pachycristatus by Untargeted UPLC-ESI-HRMS/MS and Genome Mining

Abstract

Aspergillus pachycristatus is an industrially important fungus for the production of the antifungal echinocandin B and is closely related to model organism A. nidulans. Its secondary metabolism is largely unknown except for the production of echinocandin B and sterigmatocystin. We constructed mutants for three genes that regulate secondary metabolism in A. pachycristatus NRRL 11440, and evaluated the secondary metabolites produced by wild type and mutants strains. The secondary metabolism was explored by metabolic networking of UPLC-HRMS/MS data. The genes and metabolites of A. pachycristatus were compared to those of A. nidulans FGSC A4 as a reference to identify compounds and link them to their encoding genes. Major differences in chromatographic profiles were observable among the mutants. At least 28 molecules were identified in crude extracts that corresponded to nine characterized gene clusters. Moreover, metabolic networking revealed the presence of a yet unexplored array of secondary metabolites, including several undescribed fellutamides derivatives. Comparative reference to its sister species, A. nidulans, was an efficient way to dereplicate known compounds, whereas metabolic networking provided information that allowed prioritization of unknown compounds for further metabolic exploration. The mutation of global regulator genes proved to be a useful tool for expanding the expression of metabolic diversity in A. pachycristatus.

Fungal antibiotics control bacterial community diversity in the cheese rind microbiome

“…The chemistry, genetics and physiological effects of fungal specialized metabolism are widely studied and recognized, but their ecological consequences in microbiomes are largely unknown. Previous genetic and -omics approaches identified key metabolites and pathways regulated by LaeA 28,[51][52][53][54] , but these data have not been integrated into a comprehensive model for studying microbial interactions that influence community assembly. By toggling LaeA between on and off, we were able to identify one class of metabolites produced by a strongly inhibitory fungus that allows it to dramatically remodel the bacterial communities of cheese.…”