Synthetic Yeast Cell Factories for High-Level Production of Oleo-Chemicals and Advanced Biofuels

Volatile energy costs and pressure to conserve fossil fuel resources have ignited efforts to produce biofuels and renewable commodity chemicals via microbial fermentation of biomass. The fatty acid-based biofuels (fatty acids, alkanes, fatty alcohol, etc.) are considered as ideal alternative to fossil based chemicals and advanced biofuels. Though most of these molecules have been microbial synthesized,the titers remains to be largely improved for industrial process. As Saccharomyces cerevisiae is a well-studied industrial model microorganism and the overall metabolism including the lipid metabolism is well studied, it is feasible to engineer lipid metabolism for overproduction of oleo-molecules in S. cerevisiae. Here, we systemitically engineered the lipid metabolism by increasing the precursor supply, inhibition of by-product formation, and disrupting the reversal futile cycling, which enabled production of 10.4 g/L free fatty acid, the highest titer in any microorganism. Then this fatty acid overproducing strain was tailored for fatty alcohol biosynthesis by using a carboxylic acid reductase. After enhancing the fatty aldehyde reduction by engineering alcohol dehydrogenation and reduction, fatty alcohol production reached 1.5 g/L. These results provided many interesting targets for further enhancing the production of oleo-chemicals and advanced biofuels.