Efficient biosynthesis of -caryophyllene in by -caryophyllene synthase from .

H. Lév. & Vaniot is an important traditional Chinese medicinal plant known for its volatile oils, which are the main active components of , including monoterpenes, sesquiterpenes and their derivatives. Despite its medicinal significance, the biosynthesis of sesquiterpenoids in remains underexplored. In this study, we identified four -caryophyllene synthases from A high-yield -caryophyllene engineered cell factory has been built in this study. By fusing and with a flexible linker (GGGS) and enhancing metabolic flux in the MVA pathway (, , and ), we achieved a titer of -caryophyllene reached 15.6 g/L by fed-batch fermentation in a 5 L bioreactor. To our knowledge, this represents the highest reported titer of -caryophyllene in yeast to date. This study provides a valuable tool for the industrial-scale production of -caryophyllene.