A path to perpetual chemical synthesis via photocatalytic cofactor regeneration

Harnessing the power of the Sun for perpetual chemical synthesis is one of the most sustainable ways to reduce the carbon footprint in the chemical industry. In this regard, the natural photosynthetic machinery offers key insights into the sustainable production of chemical entities in a ceaseless manner. The natural process of photosynthesis couples light harvesting to produce cofactor molecules, which then participate in enzyme-driven dark cycles for continuous biocatalytic transformations. At the core of photosynthetic machinery is the constant regeneration and consumption of cofactors, which sustain the metabolic cycles continuously. Consequently, coupling the unique powers of photocatalysis and biocatalysis through cofactor shuttling emerges as an excellent opportunity for the ceaseless production of fine chemicals. The present Perspective highlights the design principles for integrating photocatalytically regenerated cofactors with natural enzymatic cycles for various chemical transformations. Further, we examine the existing limitations of the integrated system and highlight the efforts to alleviate them. Finally, we highlight the possibilities of incorporating ideas from different research fields, from material science to synthetic biology to organometallic chemistry, to develop robust cofactor-dependent photobiocatalytic systems for the perpetual synthesis of chemicals.