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

Herein, we studied the heterologous production of alpha-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 alpha-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 alpha-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 alpha-farnesene concentration of 259.98 +/- 2.15 mg/L with alpha-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 alpha-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. (C) 2016 Elsevier Ltd. All rights reserved.