Comparative chemical genomic profiling across plant-based hydrolysate toxins reveals widespread antagonism in fitness contributions
Year: 2022
Type: article
Abstract: The budding yeast Saccharomyces cerevisiae has been used extensively in fermentative industrial processes, including biofuel production from sustainable plant-based hydrolysates. Myriad toxins and stressors found in hydrolysates inhibit microbial metabolism and product formation. Overcoming these stresses requires mitigation strategies that include strain engineering. To identify shared and divergent mechanisms of toxicity and to implicate gene targets for genetic engineering, we used a chemical genomic approach to study fitness effects across a library of S. cerevisiae deletion mutants cultured anaerobically in dozens of individual compounds found in different types of hydrolysates. Relationships in chemical genomic profiles identified classes of toxins that provoked similar cellular responses, spanning inhibitor relationships that were not expected from chemical classification. Our results also revealed widespread antagonistic effects across inhibitors, such that the same gene deletions were beneficial for surviving some toxins but detrimental for others. This work presents a rich dataset relating gene function to chemical compounds, which both expands our understanding of plant-based hydrolysates and provides a useful resource to identify engineering targets.
Source: FEMS Yeast Research
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,544
Funders: National Science Foundation, U.S. Department of Energy, U.S. Department of Agriculture, Pew Charitable Trusts, Wisconsin Alumni Research Foundation, University of Wisconsin-Madison, National Institute of Food and Agriculture, Office of Science, Great Lakes Bioenergy Research Center, National Science Foundation of Sri Lanka, Division of Graduate Education, Biological and Environmental Research
Awards: GREAT LAKES BIOENERGY RESEARCH CENTER, G1592975470, G1648283888, G222180108, G2456105274, G2978055731, G3193070969, G3294506581, G3444752832, GREAT LAKES BIOENERGY RESEARCH CENTER, Collaborative Research: RoL: The Evolution of the Genotype-Phenotype Map across Budding Yeasts, G4370329050, GREAT LAKES BIOENERGY RESEARCH CENTER, G455569901, G4747554312, G478501168, G5060370468, G5078257573, DIMENSIONS: Collaborative Research: The Making of Biodiversity Across the Yeast Subphylum, G5983990188, G608929229, G7157814893, G7350903426, TAS::89 0227:: TAS RECOVERY ACT - BIOENERGY RESEARCH CENTER CAPITAL EQUIPMENT - GLBRC, TAS::89 0227:: TAS RECOVERY ACT - BIOENERGY RESEARCH CENTER CAPITAL EQUIPMENT - GLBRC, GREAT LAKES BIOENERGY RESEARCH CENTER, G8794194214
OpenAlex ID: W4288040354