Heterologous production of α-farnesene in metabolically engineered strains of Yarrowia lipolytica

Herein, we studied the heterologous production of α-farnesene, a valuable sesquiterpene with various biotechnological applications, by metabolic engineering of Yarrowia lipolytica. Different overexpression vectors harboring combinations of tHMG1, IDI, ERG20 and codon-optimized α-farnesene synthase (OptFS) genes were constructed and integrated into the genome of Y. lipolytica Po1h. The engineered strain produced 57.08 ± 1.43 mg/L of α-farnesene corresponding to 20.8-fold increase over the initial production of 2.75 ± 0.29 mg/L in the YPD medium in shake flasks. Bioreactor scale-up in PM medium led to α-farnesene concentration of 259.98 ± 2.15 mg/L with α-farnesene to biomass ratio of 33.98 ± 1.51 mg/g, which was a 94.5-fold increase over the initial production. This first report on α-farnesene synthesis in Y. lipolytica lays a foundation for future research on production of sesquitepenes in Y. lipolytica and other closest yeast species and will potentially contribute in its industrial production.