Pathway engineering and medium optimization for alpha-farnesene biosynthesis in oleaginous yeast Yarrowia lipolytica

摘要

Farnesene is a typical sesquiterpene with applications as fragrance, flavor and precursor for the synthesis of vitamin E/K1. In this study, a series of strategies were employed to facilitate ?-farnesene accumulation in Yarrowia lipolytica . Among them, the promoter optimization of OptFSLERG20 , Sc-tHMG1 and IDI resulted in more than 62 % increase in ?-farnesene production. Together with the overexpression of Yl-HMGR and ERG19 , ?- farnesene content was signi ficantly improved by more than 3.5 times. The best metabolic engineered strain obtained was therefore used for a uniform design in shake flasks to determine the optimal medium compositions. Furthermore, a maximum ?-farnesene production of approximately 2.57 g/L (34 mg/g DCW) was obtained in fed -batch fermentation where glycerol was supplemented as the feeding carbon source when initial glucose was depleted. This study has laid a good foundation for the development of Y. lipolytica as a promising chassis microbial cell for heterologous biosynthesis of ?-farnesene and other sesquiterpenes.