(-)-α-Bisabolol is a plant-derived sesquiterpene derived from Eremanthus erythropappus,which can be used as a raw material in cosmetics and has anti-inflammatory function.In this study,we designed six mutation sites ...(-)-α-Bisabolol is a plant-derived sesquiterpene derived from Eremanthus erythropappus,which can be used as a raw material in cosmetics and has anti-inflammatory function.In this study,we designed six mutation sites of the(-)-α-bisabolol synthase BOS using the plmDCA algorithm.Among these,the F324Y mutation demonstrated exceptional performance,increasing the product yield by 73%.We constructed a de novo(-)-α-bisabolol biosynthesis pathways through systematic synthetic biology strategies,including the enzyme design of BOS,selection of different linkers in fusion expression,and optimization of the mevalonate pathway,weakening the branching metabolic flow and multi-copy strategies,the yield of(-)-α-bisabolol was significantly increased,which was nearly 35-fold higher than that of the original strain(2.03 mg/L).The engineered strain was capable of producing 69.7 mg/L in shake flasks.To the best of our knowledge,this is the first report on the biosynthesis of(-)-α-bisabolol in Komagataella phaffii,implying this is a robust cell factory for sustainable production of other terpenoids.展开更多
基金supported by the key scientific research and development project of Zhejiang Province(2024SSYS0103)the Start-up funds of Xianghu Laboratory(2023C4S02002)the National Natural Science Foundation of China(32301255)。
文摘(-)-α-Bisabolol is a plant-derived sesquiterpene derived from Eremanthus erythropappus,which can be used as a raw material in cosmetics and has anti-inflammatory function.In this study,we designed six mutation sites of the(-)-α-bisabolol synthase BOS using the plmDCA algorithm.Among these,the F324Y mutation demonstrated exceptional performance,increasing the product yield by 73%.We constructed a de novo(-)-α-bisabolol biosynthesis pathways through systematic synthetic biology strategies,including the enzyme design of BOS,selection of different linkers in fusion expression,and optimization of the mevalonate pathway,weakening the branching metabolic flow and multi-copy strategies,the yield of(-)-α-bisabolol was significantly increased,which was nearly 35-fold higher than that of the original strain(2.03 mg/L).The engineered strain was capable of producing 69.7 mg/L in shake flasks.To the best of our knowledge,this is the first report on the biosynthesis of(-)-α-bisabolol in Komagataella phaffii,implying this is a robust cell factory for sustainable production of other terpenoids.
