Synthesis of the Prospective Anticancer Molecule Perillic Acid from Orange Essential Oil by the Yeast Yarrowia lipolytica

The bioconversion of the hydrophobic and volatile limonene to perillic acid, a potential anticancer agent, by the yeast Yarrowia lipolytica was studied in two steps. Firstly, experimental design was used for process optimization using high-purity limonene as substrate and secondly orange essential oil containing 89.1% limonene was used as substrate under the previously optimized conditions. Limonene concentration and pH were identified by fractional factorial design as significant factors and were optimized by central composite design. Under optimized process conditions (0.16% (v/v) limonene; pH 6.9), the 24 h biotransformation process resulted in the accumulation of 0.368 g·L-1 of perillic acid corresponding to a molar yield of 23.1%. A subsequent substrate addition under the same reaction conditions doubled perillic acid concentration to 0.793 g·L-1 and a molar yield of 24.2%. The use of orange essential oil under the optimized reaction conditions increased both perillic acid accumulation and yield to 0.872 g·L-1 and 29.7%, respectively. The robustness of Y. lipolytica allowed the efficient biotransformation of a crude by-product of the citrus industry into a valuable fine chemical.