Genetically targeted photocatalytic organic dyes for spatiotemporally controlled organic synthesis in specific living cells

Abstract

The catalytic synthesis of many abiotic organic compounds is beyond the native capabilities of mammalian cells. Broadening the range of physiologically compatible, bond-forming catalytic reactions could enable the in situ synthesis of diverse molecules within living systems. By controlling these reactions in both specific cells and in physical space, this approach could offer transformative ways to modulate cellular behaviour and treat cells as distinct reaction vessels within organisms. Here we use genetic targeting to incorporate organic photocatalytic dyes onto and within cells to enable cell-type-specific and spatially defined catalysis. Photocatalysis can be restricted to individual cells using mild, green-to-red visible stimulation. The dyes catalyse cross-dehydrogenative C–H functionalization for the light- and cell-specific construction of C–C bonds in situ. Nuclear-localized assembly directs protein translocation with reversed transport directionality, illustrating the utility of this approach to both generate and enhance the function of chemical biology tools. We anticipate that the integration of synthetic catalysts with cell-specific targeting may lay an important foundation for future precision-directed abiotic chemical synthesis in living organisms. Adapting abiotic catalysis to living cells broadens the scope of in situ non-natural synthesis, but it is challenging to achieve synthetic versatility at cellular-level spatiotemporal organization. Now organic dyes have been shown to perform light- and genetically patternable photocatalytic synthesis, enabling in situ C–H functionalization and the construction of ligands for protein translocation.