Natural photosynthesis harnesses solar energy to convert CO 2 and water to value-added chemical products for sustaining life. We present a hybrid bioinorganic approach to solar-to-chemical conversion in which sustainable electrical and/or solar input drives production of hydrogen from water splitting using biocompatible inorganic catalysts. The hydrogen is then used by living cells as a source of reducing equivalents for conversion of CO 2 to the value-added chemical product methane. Using platinum or an earth-abundant substitute, α-NiS, as biocompatible hydrogen evolution reaction (HER) electrocatalysts and Methanosarcina barkeri as a biocatalyst for CO 2 fixation, we demonstrate robust and efficient electrochemical CO 2 to CH 4 conversion at up to 86% overall Faradaic efficiency for ≥7 d. Introduction of indium phosphide photocathodes and titanium dioxide photoanodes affords a fully solar-driven system for methane generation from water and CO 2 , establishing that compatible inorganic and biological components can synergistically couple light-harvesting and catalytic functions for solar-to-chemical conversion.artificial photosynthesis | solar fuels | photocatalysis | carbon dioxide fixation | water splitting M ethods for the sustainable conversion of carbon dioxide to value-added chemical products are of technological and societal importance (1-3). Elegant advances in traditional approaches to CO 2 reduction driven by electrical and/or solar inputs using homogeneous (4-16), heterogeneous (17-26), and biological (7, 27-31) catalysts point out key challenges in this area, namely (i) the chemoselective conversion of CO 2 to a single product while minimizing the competitive reduction of protons to hydrogen, (ii) long-term stability under environmentally friendly aqueous conditions, and (iii) unassisted light-driven CO 2 reduction that does not require external electrical bias and/or sacrificial chemical quenchers. Indeed, synthetic homogeneous and heterogeneous CO 2 catalysts are often limited by product selectivity and/or aqueous compatibility, whereas enzymes show exquisite specificity but are generally less robust outside of their protective cellular environment. In addition, the conversion of electrosynthetic systems to photosynthetic ones is nontrivial owing to the complexities of effectively integrating components of light capture with bond-making and bond-breaking chemistry.Inspired by the process of natural photosynthesis in which lightharvesting, charge-transfer, and catalytic functions are integrated to achieve solar-driven CO 2 fixation (32-35), we have initiated a program in solar-to-chemical conversion to harness the strengths inherent to both inorganic materials chemistry and biology (36). As shown in Fig. 1, our strategy to drive synthesis with sustainable electrical and/or solar energy input (37) interfaces a biocompatible photo(electro)chemical hydrogen evolution reaction (HER) catalyst with a microorganism that uses this sustainably generated hydrogen as an electron donor for CO 2 reduction. Impo...