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Raw LC-MS data for Drott et al., 2021 - PNAS

ABSTRACT: Fungi produce a wealth of pharmaceutically bioactive secondary metabolites (SMs) from biosynthetic gene clusters (BGCs). It is common practice for drug-discovery efforts to treat species secondary metabolomes as being well represented by a single or a small number of representative genomes. However, this approach misses the possibility that intraspecific population dynamics, such as adaptation to environmental conditions or local microbiomes, may harbor novel BGCs that contribute to the overall niche breadth of species. Using 94 isolates of Aspergillus flavus, a cosmopolitan model fungus, sampled from seven states in the United States, we dereplicate 7,821 BGCs into 92 unique BGCs. We find that more than 25% of pan-genomic BGCs show population-specific patterns of presence-absence or protein divergence. Population-specific BGCs make up most of the accessory-genome BGCs, suggesting that different ecological forces that maintain accessory genomes may be partially mediated by population-specific differences in secondary metabolism. We use ultra-high-performance high resolution mass spectrometry to confirm that these genetic differences in BGCs also result in chemotypic differences in SM production in different populations that could mediate ecological interactions and be acted on by selection. Thus, our results suggest a paradigm shift that previously unrealized population-level reservoirs of SM diversity may be of significant evolutionary, ecological, and pharmaceutical importance. Lastly, we find that several population-specific BGCs from A. flavus are present in Aspergillus parasiticus and Aspergillus minisclerotigenes and discuss how the importance of microevolutionary patterns we uncover inform macroevolutionary inferences and help to align fungal secondary metabolism with existing evolutionary theory.

INSTRUMENT(S): Thermo Scientific Q Exactive Orbitrap mass spectrometer, Thermo Scientific-Vanquish UHPLC system

ORGANISM(S): Aspergillus Minisclerotigenes (ncbitaxon:656917) Aspergillus Flavus (ncbitaxon:5059)

SUBMITTER: Milton T. Drott

PROVIDER: MSV000087134 | MassIVE | Wed Mar 31 07:47:00 BST 2021

SECONDARY ACCESSION(S): PXD025129

REPOSITORIES: MassIVE

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Project description:Diverse expression patterns for secondary metabolism gene clusters from Aspergillus flavus under different environmental conditions and in genetic mutants: Insights into regulation of cyclopiazonic acid along with aflatoxin Species of Aspergillus produce a diverse array of secondary metabolites, and recent genomic analysis predicts that these species have the capacity to synthesize many more compounds. It has been possible to infer the presence of 55 gene clusters associated with secondary metabolism in A. flavus. Presumably, secondary metabolites play important roles in the ecology of the producing species, but functions for most secondary metabolites remain unknown. Only three metabolic pathways have been associated with the predicted clusters in A. flavus. These include aflatoxin, cyclopiazonic acid (CPA), and aflatrem. To gain insight into the regulation of, and infer ecological significance for the 55 secondary metabolite gene clusters predicted in A. flavus, we examined their expression over 28 diverse conditions. Variables included culture media and temperature, fungal development, colonization of developing maize seeds, and misexpression of laeA, the global regulator of secondary metabolism. Hierarchical clustering analysis of expression profiles allowed us to categorize the gene clusters into four distinct clades. Gene clusters for the production of aflatoxins, CPA, and seven other unknown compound(s) were identified as belonging to one clade. To further explore the relationships found by gene expression analysis, aflatoxin and CPA production were quantified under five different cell culture environments known to be conducive or non-conducive for aflatoxin biosynthesis and during colonization of developing maize seeds. Results from these studies showed that secondary metabolism gene clusters have distinctive gene expression profiles. Aflatoxin and CPA were found to have unique regulation but similar enough that they would be expected to co-occur in commodities colonized with A. flavus.

Dataset Information

Raw LC-MS data for Drott et al., 2021 - PNAS

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