Exploring metal ion metabolisms to improve xylose fermentation in Saccharomyces cerevisiae

• Published in: Microbial biotechnology Vol. 14; no. 5; pp. 2101 - 2115
• Main Authors: Palermo, Gisele Cristina de Lima, Coutouné, Natalia, Bueno, João Gabriel Ribeiro, Maciel, Lucas Ferreira, Santos, Leandro Vieira
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01-09-2021; John Wiley and Sons Inc; Wiley
• Subjects: Anaerobic conditions; Biomass; Biorefineries; Cation Transport Proteins; Cellulose; Enzymes; Ethanol; Fermentation; Gene expression; Genomes; Heavy metals; Homeostasis; Iron; Kinases; Lignocellulose; Metabolic Engineering; Metabolism; Metal concentrations; Metal ions; Mutation; Productivity; Proteins; Saccharomyces cerevisiae; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae Proteins - genetics; Signal transduction; Sugar; Transcriptomes; Xylose; Yeast; Yeasts
• ISSN: 1751-7915; 1751-7915
• DOI: 10.1111/1751-7915.13887

Summary
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.
Designing high‐performance xylose‐fermenting yeasts is a key step to achieve scalable production in lignocellulose‐based biorefineries. This work explores metabolisms involved in metal homeostasis which positively affect xylose fermentation in engineered Saccharomyces cerevisiae strains. In summary, the manuscript indicated (i) the vacuolar Fe2+/Mn2+ transporter CCC1, and the protein involved in metal ion homeostasis BSD2, as promising new targets for rational metabolic engineering strategies, enhancing xylose consumption; (ii) provides a detailed molecular and physiological characterization of the best‐performing mutants connecting intracellular metal concentration levels with fermentation profiles; (iii) a temporal detailed expression profile indicating a metabolic remodeling in response to xylose, demonstrating changes in the main sugar sensing signaling pathways.