Exploring metal ion metabolisms to improve xylose fermentation in Saccharomyces cerevisiae

The development of high-performance xylose-fermenting yeast is essential to achieve feasible conversion of biomass-derived sugars in lignocellulose-based biorefineries. However, engineered C5-strains of Saccharomyces cerevisiae still present low xylose consumption rates under anaerobic conditions. Here, we explore alternative metabolisms involved in metal homeostasis, which positively affect C5 fermentation and analyse the non-obvious regulatory network connection of both metabolisms using time-course transcriptome analysis. Our results indicated the vacuolar Fe²⁺ /Mn²⁺ transporter CCC1, and the protein involved in heavy metal ion homeostasis BSD2, as promising new targets for rational metabolic engineering strategies, enhancing xylose consumption in nine and 2.3-fold compared with control. Notably, intracellular metal concentration levels were affected differently by mutations and the results were compared with positive controls isu1Δ, a Fe-S cluster scaffold protein, and ssk2Δ, a component of HOG pathway. Temporal expression profiles indicate a metabolic remodelling in response to xylose, demonstrating changes in the main sugar sensing signalling pathways.