Tuning Geraniol Biosynthesis via a Novel Decane-Responsive Promoter in Candida glycerinogenes

:geraniol is a rose-scented monoterpene with significantcommercial and industrial value in medicine, condiments, cosmetics, andbioenergy. Here, wefirst targeted geraniol as a reporter metabolite andexplored the suitability and potential ofCandida glycerinogenesas aheterologous host for monoterpenoid production. Subsequently, dual-pathwayengineering was employed to improve the production of geraniol with ageraniol titer of 858.4 mg/L. We then applied a synthetic hybrid promoterapproach to develop a decane-responsive hybrid promoter based on the nativepromoter PGAPderived fromC. glycerinogenesitself. The hybrid promoter was able to be induced byn-decane with 3.6 times highertranscriptional intensity than the natural promoter PGAP. In particular, the hybrid promoter effectively reduces the conflict betweencell growth and product formation in the production of geraniol. Ultimately, 1194.6 mg/L geraniol was obtained at the shakeflasklevel. The strong and tunable decane-responsive hybrid promoter developed in this study provides an important tool forfineregulation of toxic terpenoid production in cells.

Automated summary

Geraniol is a valuable monoterpene used in various industries. In this study, Candida glycerinogenes was explored as a host for producing monoterpenoids. Through engineering and the use of a hybrid promoter, the production of geraniol was improved. The developed decane-responsive hybrid promoter provides a useful tool for regulating terpenoid production.