Characterization of a toxic secondary metabolite cluster in Penicillium fungi (DSI-SRP)
This DSI-SRP fellowship funded Charu Balamurugan to work in the laboratory of Dr. Antonis Rokas in the Departments of Biological Sciences and Biomedical Informatics during the summer of 2022. Charu is a sophomore with majors in Biological Sciences and Medicine, Health, & Society.
This summer, Charu studied the characterization of a toxic secondary metabolite cluster in Penicillium fungi. Fungi produce a diversity of secondary metabolites, self-produced organic compounds serving survival functions, that aid in defense among other functions. Many of these secondary metabolites are encoded by a grouping of genes known as biosynthetic gene clusters (BGCs). Fungi belonging to the genus Penicillium are known to produce secondary metabolites such as the antibiotic penicillin, the mycotoxin patulin, and the cholesterol-lowering medicine mevastatin—demonstrating an immense potential for use in bioindustry and threat as a post-harvest pathogen. Aspergillus, the closest known genus to Penicillium, also produce secondary metabolites—such as gliotoxin, a mycotoxin with a vast range of known toxic effects that impair human immune cell function. Some Penicillium species, such as Penicillium lilacinoechinulatum and Penicillium decumbens, are known to produce gliotoxin; however, a characterization of the BGC responsible for gliotoxin production among Penicillium species is lacking leading to an incomplete understanding of the pathogenic potential of Penicillium species. Gliotoxin is also highly toxic for fungi that produce this secondary metabolite, resulting in the need for resistance genes (encoding transcription factors, transporters, oxidoreductases, etc.) outside the cluster, along with the gliT, encoding an oxidoreductase, within the cluster. Here we report presence and absence patterns and characterization of the gliotoxin BGC in 35 Penicillium genomes spanning species and populations. These results reveal homologous, mostly complete gliotoxin BGCs in 12 genomes, whereas homologs of resistance genes outside of the cluster are broadly conserved. Evolutionary rate analysis revealed complete BGCs are evolving at a slower rate than incomplete BGCs. Ancestral state reconstructions suggest that the ancestor of Penicillium species possessed the gliotoxin BGC. We anticipate our analysis to be a starting point for the exploration of fungal pathogen evolution as it relates to gliotoxin in these genera of important filamentous fungi.
In addition to receiving support through a DSI-SRP fellowship, this project was supported and facilitated by the DSI Data Science Team through their regular summer workshops and demo sessions.