Proteome response of two natural strains of Saccharomyces cerevisiae with divergent lignocellulosic inhibitor stress tolerance

Strains of Saccharomyces cerevisiae with improved tolerance to plant hydrolysates are of utmost importance for the cost-competitive production of value-added chemicals and fuels. However, engineering strategies are constrained by a lack of understanding of the yeast response to complex inhibitor mixtures. Natural S. cerevisiae isolates display niche-specific phenotypic and metabolic diversity, encoded in their DNA, which has evolved to overcome external stresses, utilise available resources and ultimately thrive in their challenging environments. Industrial and laboratory strains, however, lack these adaptations due to domestication. Natural strains can serve as a valuable resource to mitigate engineering constraints by studying the molecular mechanisms involved in phenotypic variance and instruct future industrial strain improvement to lignocellulosic hydrolysates. We, therefore, investigated the proteomic changes between two natural S. cerevisiae isolates when exposed to a lignocellulosic inhibitor mixture. Comparative shotgun proteomics revealed that isolates respond by regulating a similar core set of proteins in response to inhibitor stress. Furthermore, superior tolerance was linked to NAD(P)/H and energy homeostasis, concurrent with inhibitor and reactive oxygen species detoxification processes. We present several candidate proteins within the redox homeostasis and energy management cellular processes as possible targets for future modification and study. Data are available via ProteomeXchange with identifier PXD010868. Proteomic analysis provides new insight into the complexity of lignocellulosic inhibitor tolerance in natural isolates of S. cerevisiae.