Metabolic network remodelling enhances yeast’s fitness on xylose using aerobic glycolysis

The reprogramming of metabolism in response to switching the carbon source from glucose to non-preferred carbon sources is well-studied for yeast. However, understanding how metabolic networks respond to utilize a non-natural carbon source such as xylose is limited due to the incomplete knowledge of cellular response mechanisms. Here we applied a combination of metabolic engineering, systems biology and adaptive laboratory evolution to gain insights into how yeast can perform a global rewiring of cellular processes to efficiently accompany metabolic transitions. Through metabolic engineering, we substantially enhanced the cell growth on xylose after the growth on glucose. Transcriptome analysis of the engineered strains demonstrated that multiple pathways were involved in the cellular reprogramming. Through genome resequencing of the evolved strains and reverse engineering, we further identified that SWI/SNF chromatin remodelling, osmotic response and aldehyde reductase were responsible for the improved growth. Combined, our analysis showed that glycerol-3-phosphate and xylitol serve as two key metabolites that affect cellular adaptation to growth on xylose. [Figure not available: see fulltext.]