S103: Metabolic engineering for novel biosynthesis of fatty acid from carbon dioxide and hydrogen

Renewable resources such as biofuel and chemicals provide independence from petroleum.  Therefore, the ability to produce renewable energy and chemical is of great interest for environmental and economic reasons.  While much effort have been placed on using traditional feedstocks as renewable resources, the advantages of non-traditional feedstocks, such as carbon dioxide (CO₂) and hydrogen (H₂) are being recognized with recent advancement of syngas technology and for the ability to relieve the burden of competing with food sources and demand for agricultural land.  OPXBIO is currently engineering Cupriavidus necator, a facultative chemolithoautotrophic bacterium capable of utilizing CO₂ and H₂ to produce fatty acid by a novel pathway that is independent of the native fatty acid biosynthesis.  Unlike the traditional pathway that involves acyl-carrier protein fatty acid synthesis, the novel pathway consists of enzymes catalyzing a 2-carbon extension of acyl-CoA with malonyl-CoA.  The engineered strain of C. necator have been modified to 1) control the expression of heterologous enzymes involved in the novel fatty acid biosynthesis, 2) increase extender substrate by utilizing the malonyl-CoA platform technology developed at OPXBIO, 3) decrease the native fatty acid utilization, and 4) increase hydrogen uptake and carbon fixation in collaboration with NREL.  Fatty acids from C. necator have the potential for conversion into other high value chemical precursors and have been successfully catalytically converted to diesel fuel for the ARPA-e program.  The development and progress on the metabolic engineering of C. necator will be presented.