Engineering yeast to convert lignocellulose into vanillin

Valorizing lignocellulosic biomass (LCB) into platform aromatic chemicals could contribute to a sustainable biomass-based bioeconomy. However, lacking simultaneous bioconversion route of lignin and carbohydrates hinders the LCB utilization. The artificial biological funneling pathway (ABFP) was hence designed to convert full components of LCB into vanillin. The results showed that combinational engineering strategies enabled the successful accumulation of vanillin in Saccharomyces cerevisiae. The funneling pathways of lignin-derived monomers to vanillin were constructed. Enzyme fusion and S-adenosylmethionine metabolism regulation of heterologous rate-limiting enzyme further promoted the vanillin production to 2.49 and 1.94 mmol/L from ferulic acid and p-coumaric acid, respectively. The construction of funneling pathways of hexose and pentose promoted the carbon flux towards vanillin biosynthesis. Together with the regulation of branch and shikimic acid pathways, the microbial cell factory with a novel ABFP produced 1.97 mmol/L vanillin from real LCB hydrolysates with a recorded yield of 10.5 mg vanillin/g carbon source. Overall, the engineered S. cerevisiae simultaneously valorized full components into fine aromatic chemicals, holding the promise to transform biorefinery mode and contribute to the biomass-based economy.