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Synthetic pathway engineering for robustness improvement of industrial strains envisaging their use in lignocellulosic biorefineries requires the understanding of the complex molecular mechanisms underlying Saccharomyces cerevisiae tolerance to inhibitors present in hydrolysates. This study, recently published in Biotechnology for Biofuels, was led by Isabel Sá-Correia and part of Silvia F. Henriques PhD thesis in Biotechnology and Biosciences and also co-authored by Nuno P. Mira. The paper reports the identification, at a genome-wide scale, of genes whose expression confers protection or susceptibility to formic acid. This chemogenomic analysis allowed the identification of 172 determinants of tolerance and 41 determinants of susceptibility, among them HAA1, encoding the main transcriptional regulator of yeast transcriptome reprograming in response to acetic acid, and genes of the Haa1-regulon. TRK1, encoding the high-affinity potassium transporter and genes encoding positive regulators of Trk1 activity were surprisingly found among the genes that when deleted lead to increased tolerance to formic acid. It was hypothesized that Trk1 facilitates formic acid uptake into the yeast cell and demonstrated that at a saturating K+ concentrations, trk1Δ mutant is more tolerant than the parental strain. The list of genes resulting from this study provides potentially valuable information to guide improvement programs for the development of more robust strains against formic acid.
