Solar-powered P450 catalysis: Engineering electron transfer pathways from photosynthesis to P450s

With the increasing focus on green chemistry, biocatalysis is becoming more widely used in the pharmaceutical and other chemical industries for sustainable production of high value and structurally complex chemicals. Cytochrome P450 monooxygenases (P450s) are attractive biocatalysts for industrial application due to their ability to transform a huge range of substrates in a stereo- and regiospecific manner. However, despite their appeal, the industrial application of P450s is limited by their dependence on costly reduced nicotinamide adenine dinucleotide phosphate (NADPH) and one or more auxiliary redox partner proteins. Coupling P450s to the photosynthetic machinery of a plant allows photosynthetically-generated electrons to be used to drive catalysis, overcoming this cofactor dependency. Thus, photosynthetic organisms could serve as photobioreactors with the capability to produce value-added chemicals using only light, water, CO₂ and an appropriate chemical as substrate for the reaction/s of choice, yielding new opportunities for producing commodity and high-value chemicals in a carbon-negative and sustainable manner. This review will discuss recent progress in using photosynthesis for light-driven P450 biocatalysis and explore the potential for further development of such systems.