Engineering Yarrowia lipolytica for sustainable production of the chamomile sesquiterpene (-)-α-bisabolol

The sesquiterpene (-)-alpha-bisabolol has been shown to have antibacterial, antiseptic, and anti-inflammatory activities, as well as skin-soothing properties, which has led to its wide use in cosmetics. However, the current production of (-)-alpha-bisabolol via steam-distillation of plants is not sustainable and cannot meet the increasing market demand. In the present study, a sustainable strategy for (-)-alpha-bisabolol production was developed by constructing a Yarrowia lipolytica cell factory. The oleaginous yeast Y. lipolytica has a native mevalonate pathway and strong acetyl-CoA flux, which can supply adequate precursors for (-)-alpha-bisabolol production. The endogenous mevalonate pathway and heterologous (-)-alpha-bisabolol synthesis pathway were optimized by strengthening the rate-limiting enzymes, downregulating competing pathway, as well as balancing the distribution of the common precursor acetyl-CoA between endogenous lipids and heterologous (-)-alpha-bisabolol synthesis by strengthening the beta-oxidation pathway. Finally, (-)-alpha-bisabolol production of up to 364.23 mg L-1 was achieved in batch culture. This sustainable method has potential for industrial (-)-alpha-bisabolol production.

Automated summary

The sesquiterpene (-)-alpha-bisabolol has various beneficial properties and is widely used in cosmetics, but the current production method is not sustainable. This study successfully developed a sustainable strategy for (-)-alpha-bisabolol production by constructing a Yarrowia lipolytica cell factory, achieving a high yield of the compound in batch culture.