Metabolic engineering of saccharomyces cerevisiae for 3-hydroxypropionic acid production

3-Hydroxypropionic acid (3-HP) is an important building block chemical that can be produced from renewable resources through the malonyl-CoA pathway. This route is the best candidate for 3-HP biosynthesis through the expression of the malonyl-CoA reductase (MCR). However, the problem of the imbalance between MCR-C and MCR-N proteins causes a low conversion rate of malonyl-CoA to 3-HP. Therefore, this study aimed to balance the bi-functional MCR enzyme by dissecting MCR into two fragments and enhancing the supply of intermediates to increase the production of 3-HP. It was found that the recombinant harboring dissected MCR produced 1.26 g/L of 3-HP, which improved the 3-HP titer 21-fold in comparison with the strain carrying the full-length MCR gene. The addition of cerulenin and acetate to the fermented medium enhanced 3-HP yield by 8 times and recombinant yeast produced 3-HP up to 10 g/L (0.21 gproduct/gglucose). The results of using agricultural products and waste represented that sugarcane juice was an outstanding feedstock in which the recombinant generated 8.23 g/L of 3-HP with a yield of 0.12 gproduct/gglucose from 60% sugarcane juice. While the 3-HP concentration of 7.51 g/L was obtained using 30% molasses as a carbon source. The utilization of rice straw hydrolysate as a carbon source indicated that S. cerevisiae S2 produced 3-HP of 4.02 g/L, which was 0.074 gproduct/gglucose in the diluted hydrolysate. These findings provide an alternative and sustainable strategy for utilizing agricultural biomass and byproducts for 3-HP production, which is a good foundation for industrial scale in the future.