A new computational framework created by Oak Ridge National Laboratory researchers is accelerating their understanding of who’s in, who’s out, who’s hot and who’s not in the soil microbiome, where fungi often act as bodyguards for plants, keeping friends close and foes at bay. 

The research is shining a light on specialized fungal metabolites, small molecules produced by fungi that can help or harm plants and other organisms. These metabolites can, for instance, help bioenergy plants like the poplar tree thrive in harsh growing conditions and store more carbon belowground. Fungal metabolites are also used by humans to make everything from food additives such as citric acid to drugs to fight bacterial infections and cancer, and as pesticides and herbicides for agriculture.

The gene clusters in fungi that produce specialized metabolites are usually silent in standard laboratory cultures until signaled by external compounds or environmental conditions. ORNL scientists wanted to analyze the interactions of compounds like lipids and chitins on metabolite production in fungi to improve the accumulation of these natural products. 

Using a data-driven approach described in the journal PNAS Nexus, ORNL scientists were able to predict which substances would best stimulate fungal metabolites, then validated the findings in the lab using cultures of the mold Aspergillus fumigatus, mass spectrometry analysis and comparison to published datasets. The approach greatly speeds the painstaking process typically deployed to identify, extract and characterize specialized metabolites.

The modeling framework leverages graph theory, a machine learning approach that analyzes the complex relationships in processes such as the interactions of microbes with each other and with plants. “By using graph theory, we can better identify the chemical signals that trigger certain metabolites in fungi, and we can also use it to narrow down which fungal species are important to analyze,” said Muralikrishnan (Murali) Gopalakrishnan Meena, computational scientist at ORNL’s National Center for Computational Sciences. 

The research is part of the Plant-Microbe Interfaces Scientific Focus Area at ORNL, a project sponsored by the Department of Energy’s Office of Science Biological and Environmental Research program that aims to better understand the mutually beneficial relationships between plants and microbes in the plant root environment known as the rhizosphere. That information can then be used to address challenges related to bioenergy, environmental remediation and soil carbon storage. 

The SFA is largely focused on poplar — a key biomass crop being studied at ORNL for bioenergy production. “We want to understand the effects of metabolites, organisms and compounds on poplar — its roots, stems, leaves, the entire microbiome,” said Tomás Rush, a mycologist in ORNL’s Biosciences Division who co-led the project.

Some fungi like A. fumigatus, a microbe important to carbon cycling found in the poplar rhizosphere, are good at identifying both threats and benefactors in the soil microbiome that can affect plant hosts, Rush said.