Metabolic Engineering of Fatty Acid Downstream Pathway in Saccharomyces Cerevisiae to Produce Olechemicals

With the rapid development of synthetic biology and metabolic engineering, microbial production of biofuels has become an attractive alternative instead of traditional fossil fuels. The budding yeast Saccharomyces cerevisiae as a robust model microorganism is widely used in metabolic engineering. Here, we engineered downstream pathway of fatty acid to produce fatty acid-derived chemicals in S. cerevisiae. First, we constructed a more effective downstream pathway to directly converted FFAs to alkene by an appropriate P450 and overexpressed ACC1 gene (acetyl-CoA carboxylase) simultaneously to increase the production of malonyl-CoA. Besides, we also designed another self-sufficient P450 to produce terminal hydroxyl fatty acid by FFAs and could be further converted to amino fatty acid which is a monomer for an important synthetic fibre-nylon. At last, FFAs were firstly reduced to fatty aldehyde and then further converted to alkane by ADO. Fusion expression of ADO with alternative electron transfer system could efficiently converted fatty aldehyde to alkane in S. cerevisiae. The production of fatty acid-derived chemicals (alkene, hydroxyl fatty acid and alkane) was significantly improved by the three optimized pathways in S. cerevisiae that provides an efficient and economic route to the important target chemicals.