Bioderivatization as a concept for renewable production of toxic or poorly soluble chemicals

Abstract

Bio-based production has increasingly gained attention as an alternative technology to complement or even substitute petroleum-based production of valuable chemicals. This technology, however, relies on the use of microbial cell factories and at times faces several challenges, including toxicity of the target products to microbial hosts. Many plants and microorganisms are naturally capable of biosynthesizing toxic molecules, but they often convert them into derivatives with reduced toxicity or enhanced solubility before the molecules are stored or excreted. Inspired by this principle, a novel strategy, bioderivatization, was proposed. Bioderivatization is here defined as a purposeful biochemical derivatization of intended target molecules by altering the functional groups to overcome such challenges. Oacetylation and O-glucosylation were proposed and investigated as two bioderivatization strategies. As a proof-of-principle, the effect of bioderivatization on biosynthesis of a relatively toxic and poorly soluble chemical, 1-octanol, was evaluated. The existing 1-octanol pathway was first optimized to enable the production of 1-octanol at higher titer. Novel synthetic pathways to derivatize 1-octanol into octyl acetate and octyl glucoside were then implemented in Escherichia coli and cyanobacteria. The evaluation of bioderivatization on growth and productivity showed that the implementation of bioderivatization contributed to improved growth and/or productivity in most cases. To understand if the bioderivatization strategy can be implemented in a broader scope (i.e., to derivatize other toxic chemicals), this strategy was also applied to derivatize several other attractive chemicals from different chemical classes. The preliminary results successfully identified several potential chemical candidates, including 1-dodecanol, menthol, and eugenol that showed a higher degree of toxicity compared to their corresponding derivatives. Finally, this study was concluded by identification of several active key enzymes to derivatize these toxic compounds. Altogether, this study showed that bioderivatization could be considered a strategy to improve the bioproduction of toxic or poorly soluble chemicals.