Systematic Engineering of Lipid Metabolism for Fatty-Acid-Based Biofuel Production

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 (FABB, biodiesel, alkanes, alcohol, etc.) are considered as ideal alternative fuels for high-power machines as well as materials for biochemical synthesis due to their high energy density and environmental friendliness. Though several FABB molecules have been microbialy synthesized,the titers remains to be largely improved for industrial process. The natural oleaginous microorganisms can accumulate cellular lipid to more than 60% (w/w) of dry cell weight, however, the scarcity of genetic tools and metabolic intractability prevent their engineering for lipid derived FABB production. As Saccharomyces cerevisiae is a well-studied industrial model microorganism and the overall metabolism in S. cerevisiae, including the lipid metabolism is well studied, it is feasible to engineer an intracellular lipid biosynthesis pathway for FABB overproduction into S. cerevisiae. Therefore, nature inspired reconstruction of the lipid metabolism regulation of oleaginous microorganism in S. cerevisiae should provide a novel platform for FABB production. According to the tans-omics study in the candidate’s former lab, we partition the overall reconstructed FABB biosynthesis into four modules: module 1, upstream/precursor; module 2, relative pathways for lipid anabolism and catabolism; module 3, downstream modification module for FABB synthesis from the lipid intermediates; module 4, regulation module. We will increase and balance metabolic flux to FABB biosynthesis by the multivariate engineering of the modules. The multidisciplinary and inter-sectorial approach of this project will create conditions for high yield conversion of biomass into target biofuels, inhibition of by-product formation (e.g. ethanol) and improvement of FABB productivity