Effectiveness of recombinant Escherichia coli for the production of (R)-(+)-perillyl alcohol 

Abstract

Background:(R)-(+)-perillyl alcohol is a naturally oxygenated monoterpene that is produced in perilla leaves, citrus, lemon and lavender. Perillyl alcohols have many uses, including natural flavor additives, insecticides, jet fuels and anti-cancer therapies. The bioconversion of readily available monoterpene precursors, such as (R)-(+)-limonene are recognized as valuable oxygenated derivatives. However, as this natural product is present at low concentrations in plant oils, alternative microbial production methods are required for its extraction from natural plant sources. Results:In this study, we engineered Escherichia coli to possess a heterologous mevalonate (MVA) pathway, including limonene synthase, P-cymene monoxygenase hydroxylase and P-cymene monoxygenase reductase for the production of (R)-(+)-perillyl alcohol. The concentration of (R)-(+)-limonene (the monoterpene precursor to (R)-(+)-perillyl alcohol) reached 27.3 mg/L from glucose. Enhanced (R)-(+)-perillyl alcohol production was therefore achieved. The strain produced (R)-(+)-perillyl alcohol at a titer of 45.7 mg/L in a 5 L bioreactor fed batch system. Conclusions:These data highlight the efficient production of (R)-(+)-perillyl alcohol through microbial fermentation. This can serve as a platform for the future production of other monoterpenes.