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Gumilang, A.

Publications and source records attributed to Gumilang, A..

2 recordsLinked to original sources

An integrative genomic and chemical similarity approach linking fungal secondary metabolites and biosynthetic gene clusters

Fungi are well known to biosynthesize structurally complex secondary metabolites (SMs) with diverse bioactivities. These fungal SMs are frequently produced by biosynthetic gene clusters (BGCs). Linking SMs to their BGCs is key to understanding their chemical and biological functions. Reasoning that structural similarity of SMs arises from similarities in the genes involved in their biosynthesis, we developed an integrative approach that leverages known BGC-SM pairs to predict global links across SMs and BGCs in fungi. As proof of concept, we systematically interrogated metabolomes and genomes of 16 strains of the filamentous fungus Aspergillus fischeri, detecting a total of 60 metabolites. Of those, we were able to assign 22 to known BGC-SM pairs and propose specific hypotheses for the remaining 38 metabolites. These results suggest that coupling genomic similarity and chemical structure-based similarity is a straightforward and high-throughput approach for linking fungal SMs to their BGCs.

microbiology↗

Strain heterogeneity in a non-pathogenic fungus highlights factors contributing to virulence

Fungal pathogens exhibit extensive strain heterogeneity, including variation in virulence. Whether closely related non-pathogenic species also exhibit strain heterogeneity remains unknown. Here, we comprehensively characterized the pathogenic potentials (i.e., the ability to cause morbidity and mortality) of 16 diverse strains of Aspergillus fischeri, a non-pathogenic close relative of the major pathogen Aspergillus fumigatus. In vitro immune response assays and in vivo virulence assays using a mouse model of pulmonary aspergillosis showed that A. fischeri strains varied widely in their pathogenic potential. Furthermore, pangenome analyses suggest that A. fischeri genomic and phenotypic diversity is even greater. Genomic, transcriptomic, and metabolomic profiling identified several pathways and secondary metabolites associated with variation in virulence. Notably, strain virulence was associated with the simultaneous presence of the secondary metabolites hexadehydroastechrome and gliotoxin. We submit that examining the pathogenic potentials of non-pathogenic close relatives is key for understanding the origins of fungal pathogenicity.

evolutionary biology↗