Integrated Biotic–Abiotic Solar Driven NADPH Regeneration Platform in Escherichia coli for Chemical Biomanufacturing Applications

Abstract The development of a biohybrid bacterium capable of self‐synthesizing photocatalytically active quantum dots (QDs) is reported using the expression of a template protein that dictates the QDs size and properties. This biotic–abiotic light‐harvesting module is utilized for solar‐driven NADPH regeneration within the living bacteria, facilitated by controlled expression of ferredoxin NADP + reductase. It is shown that the co‐expression of the latter is crucial for the selective production of biologically active 1,4‐NADPH. Upon irradiation, an 8.5‐fold increase in intracellular NADPH/NADP + levels is shown, creating a pool of reducing equivalents available for reductive biocatalysis. This module is then utilized for the activation of a solar‐driven synthetic cascade by co‐expressing the NADPH‐dependent imine reductase responsible for the generation of precious chiral amines. It is shown that the addition of a diffusing redox mediator is essential for maximizing cell performance. These results present a promising route toward the development of semi‐artificial photosynthetic processes in living cells.