Fusarium Protein Toolkit: A web-based resource for structural and variant analysis of Fusarium species

Authors: Kim, Hye-Seon; HALEY, OLIVIA - Orise Fellow; Portwood, John; Harding, Stephen; Proctor, Robert; Woodhouse, Margaret; Sen, Taner; Andorf, Carson

Submitted to: BMC Microbiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/27/2024
Publication Date: 9/6/2024
Citation: Kim, H., Haley, O., Portwood Ii, J.L., Harding, S.F., Proctor, R., Woodhouse, M.H., Sen, T.Z., Andorf, C.M. 2024. Fusarium Protein Toolkit: A web-based resource for structural and variant analysis of Fusarium species. BMC Microbiology. https://doi.org/10.1186/s12866-024-03480-5.
DOI: https://doi.org/10.1186/s12866-024-03480-5

Interpretive Summary: The fungus Fusarium causes billions of dollars in losses to world agriculture annually by causing destructive crop diseases and contaminating infected crops with toxins that are health hazards to humans and livestock. Fusarium and other fungi typically have the genetic blueprints for over 10,000 proteins, each with an important role in one or more biological processes. Very little is known about which proteins produced by Fusarium contribute to its ability to cause crop diseases and toxin contamination. To address this critical knowledge gap, ARS researchers in Peoria, Illinois, and Ames, Iowa, developed an interactive online database that has computer-generated models for all proteins produced by 22 Fusarium species. The interactive nature of the database allows users to investigate predicted structures and functions of the proteins, including how they could contribute to the ability of Fusarium to infect crops. The database also allows users to investigate whether small differences in the same protein can impact function. The database will aid identification of Fusarium proteins that can be used to develop control strategies that reduce crop diseases and toxin contamination caused by the fungus.

Technical Abstract: 1) Background: The fungal genus Fusarium poses significant threats to food security and safety worldwide because it includes numerous species that cause destructive diseases and/or mycotoxin contamination of crops. The adverse effects of climate change exacerbate some existing threats and cause new problems. These challenges highlight the need for innovative solutions, including development of advanced tools to identify targets to control crop diseases and mycotoxin contamination incited by Fusarium. 2) Description: In response to these challenges, we developed the Fusarium Protein Toolkit (FPT) to allows users to interrogate the structural and variant landscape within the Fusarium pan-genome. FPT offers a comprehensive approach for understanding and mitigating detrimental effects of Fusarium on agriculture. FPT displays both AlphaFold and ESMFold-generated 3D structure models of proteins from six Fusarium species. The protein structures are accessible through a user-friendly web portal and facilitate comparative analysis, functional annotation inference, and identification of related protein structures. Using the protein language model Evolutionary Scale Modeling, FPT predicts the impact of over 270 million coding variants in two of the most agriculturally important species, Fusarium graminearum, which causes Fusarium head blight and trichothecene mycotoxin contamination of cereals, and F. verticillioides, which causes ear rot and fumonisin mycotoxin contamination of maize. To facilitate assessment of naturally occurring genetic variation, FPT provides variant effect scores for proteins in a Fusarium pan-genome constructed from 22 diverse species. The scores indicate potential functional consequences of amino acid substitutions and are displayed as intuitive heatmaps using the PanEffect framework. 3) Conclusion: FPT fills a knowledge gap by providing previously unavailable tools to assess structural and missense variation in proteins produced by Fusarium, the most agriculturally important group of mycotoxin-producing, plant pathogens. FPT will not only deepen our understanding of pathogenic mechanisms in Fusarium, but it will also aid identification of genetic targets that can be used to develop control strategies that reduce crop diseases and mycotoxin contamination. Such targets are vital to solve the agricultural problems incited by Fusarium, particularly evolving threats affected by climate change. By providing a novel approach to interrogate Fusarium-induced crop diseases, FPT is a crucial step toward safeguarding food security and safety worldwide.