Rational design strategies for functional reconstitution of plant cytochrome P450s in microbial systems

Abstract

Plant natural products (NPs) are of pharmaceutical and agricultural significance, yet the low abundance is largely impeding the broad investigation and utilization. Microbial bioproduction is a promising alternative sourcing to plant NPs. Cytochrome P450s (CYPs) play an essential role in plant secondary metabolism, and functional reconstitution of plant CYPs in the microbial system is one of the major challenges in establishing efficient microbial plant NP bioproduction. In this review, we briefly summarized the recent progress in rational engineering strategies for enhanced activity of plant CYPs in Escherichia coli and Saccharomyces cerevisiae, two commonly used microbial hosts. We believe that in-depth foundational investigations on the native microenvironment of plant CYPs are necessary to adapt the microbial systems for more efficient functional reconstitution of plant CYPs.

Figure 1

Functional reconstitution of plant cytochrome P450s (CYPs) for producing phytochemicals in microbes. Many strategies have been developed to improve the activity of recombinant CYPs in microbes. Some working mechanisms of these strategies have been proposed and further study is needed to validate them. *These strategies are reviewed elsewhere [11,24]. Process conditions (temperature, pH, etc.) affect CYP activity through multiple mechanisms and are reviewed elsewhere [24]. CPR: CYP reductase.