Combined bioderivatization and engineering approach to improve the efficiency of geraniol production

Abstract

Constructing microbial factories offers a sustainable strategy for terpenoid synthesis; however, the accumulation of terpenoid products is often toxic to cells and hampers production yields. Here, we developed a bioderivatization strategy that successfully alleviates the toxicity of the end-product and maximizes the biochemical production of geraniol in Escherichia coli. We observed that the conversion of geraniol to less toxic geranyl acetate, which is an esterified derivative of geraniol, had a significant positive effect on productivity. Subsequently, the high concentration and purity of geraniol was recovered by the combined hydrolysis of geranyl acetate and solid phase adsorption. These findings demonstrate that a combination of bioderivatization and engineering approaches for the biosynthesis of a relatively toxic chemical (geraniol) can mitigate cytotoxicity while further promoting production efficiency. Finally, the maximal titer of these engineering strategies accumulated 13.19 g L⁻¹ of geraniol by fed-batch fermentation in a 10-L fermentor. This study highlights the ability of this system to address the challenges associated with toxic geraniol accumulation. More broadly, the developed approach could also be considered for metabolic engineering of other similar chemicals.