Constructing artificial methylotrophic Saccharomyces cerevisiae for chondroitin sulfate production using a multidimensional combinatorial strategy
The concept of a methanol-based circular bioeconomy envisions the conversion of greenhouse gases into one-carbon compounds, which are subsequently utilized to produce high-value-added products. However, the toxicity of intermediates limits the metabolic efficiency within chassis strains. Here, a carbon metabolism reconfiguration strategy combined with adaptive laboratory evolution (ALE) was applied to engineer an artificial methylotrophic yeast by accelerating the flux of toxic intermediates into the central carbon metabolism. After modifying the key gene Sfa1 identified by ALE and introducing a light-responsive switch to dynamically redirect the carbon flux,