Biologically synthesized 10-Hydroxy-2-Decenoic acid activates cornified envelope formation via PPARα signaling, and regulates oxidative respiratory chain to improve mitochondrial function

10-Hydroxy-2-decenoic acid is a trans-unsaturated fatty acid exclusively found in royal jelly, known for its health and medical benefits. The current isolation and preparation methods have limitations such as low yield, high costs, difficult operation, and mixed products, which hinder its wider application. This study introduced P450 enzyme fusion gene into S. cerevisiae BY4741, then fermenting trans-2-decenoic acid could produce 10-Hydroxy-2-decenoic acid. With the biosynthesized 10-Hydroxy-2-decenoic acid, we explored its potential application in skin care. Transcriptomic results suggested that 10-Hydroxy-2-decenoic acid promoted epidermal barrier function and dermal energy metabolism. In vitro experiments revealed that within the epidermal layer, 10-Hydroxy-2-decenoic acid activated PPARα signaling and enhanced the expression of downstream genes IVL, LOR, FLG, and TGM1, thereby promoting epidermal differentiation. It upregulated the expression of SPT, GBA, and ACACA, increasing intercellular lipid content and accelerating the formation of the cornified envelope. In the dermal layer, 10-HDA is capable of enhancing the mitochondrial membrane potential, reinforcing the proton gradient, thereby increasing the efficiency of the coupled electron transport chain and leading to the generation of more ATP. It also upregulates NADPH, providing a certain level of reductive power to reduce the production of oxidative by-products, improving mitochondrial functional efficiency. Taken together, these findings indicated that in addition to its application in food and health products, biologically synthesized 10-Hydroxy-2-decenoic acid could serve as an effective skincare ingredient, contributing to skin barrier repair and resistance against skin aging. However, the deeper mechanism by which 10-HDA functions still needs to be further explored.