Rewiring Central Carbon Metabolism For Fatty Acid Production In Saccharomyces Cerevisiae

The huge consumption of energy and the shortage of fossil fuels makes it difficult to maintain the sustainable development of the economy.Finding renewable energy sources that can replace fossil fuels is an urgent problem at present.Biosynthesis of fatty acids provides alternative bioenergy due to their high energy density and high matching with traditional energy sources.Saccharomyces cerevisiae has been used in many aspects as cell factories.In this project,metabolic pathways of Saccharomyces cerevisiae were modified to increase fatty acid production.We used the fatty acid producing strain YJZ08 as the background strain which knocked out the competitive pathways of fatty acid production?Faal,Faa4,Pox1 and Hfd1?.First,we introduced the exogenous NADPH synthesis pathway?GapN?and deleted glycerol synthesis pathway?Gpd1,Gpd2?to regulate the redox balance in cells.Secondly,the introduction of exogenous cytosolic acetyl-CoA synthesis pathways,including PDH pathway and PK pathway,is intended to increase the production of fatty acid synthesis precursor acetyl-CoA.Besides,we discussed the effects of the regulation of lipid metabolism?Pahl,Dpp1,Lpp1 and Are1?.Finally,we test the effects of various strategies working together.Through the implementation of different strategies,fatty acid production increased.The strain with highest yield is PDH₅ which introduced the PDH pathway and deleted Gpd1,Gpd2,PAH1,LPP1,DPP1 and ARE1.The yield of fatty acids in batch fermentation reached 153.6 mg/L/OD600 which was 2.5 folds of YJZ08.