Genetically-targeted photocatalytic organic dyes for spatiotemporally controlled organic synthesis directed by specific living cells

Catalytic reactions of a broad range of abiotic molecules and macromolecules are beyond the native capabilities of mammals. Natural enzymes from prokaryotes or plant-based eukaryotes have limited substrate scopes. Therefore, broadening the range of catalytic bond-forming reactions that function in physiological conditions would enable the syntheses of a vast array of molecules directly within biological systems. This approach may provide an alternative way to modulate cellular behaviors if such molecules can be synthesized with spatiotemporal control on specific cell types in living systems; furthermore, restricting synthesis to well-defined cells or cell-types would enable a potentially transformative approach of treating cells as separable reaction vessels within living organisms. Herein, we use genetic targeting to incorporate an organic photocatalytic dye onto specific cell types to enable in-situ light-controlled and spatially defined chemical synthesis of non-natural molecules. We demonstrate, for the first time, a photo-patterned organic coupling reaction in the extracellular matrix of living cells under dilute, aqueous, aerobic physiological conditions. A 6-fold contrast in reaction yield can be achieved between two adjacent HEK293FT cells with and without light exposure. The above photocatalysis can be initiated using mild confocal laser stimulation as low as 16 μW/mm2 at multiple wavelengths. Furthermore, the cell-type specific photocatalyzed C-H functionalization coupling reactions taking place on cell surfaces are used to demonstrate anabolic construction of non-natural products. The above findings lay an important foundation for developing future abiotic cell-type specific chemical syntheses in living organisms.