Here, we introduce the rational design of OPVs for sustainable and direct semi-artificial photosynthesis, driving unassisted fuel synthesis for up to 1 day. To this end, BHJ-based OPVs are interfaced with hierarchically nanostructured inverse opal TiO2 (IO-TiO2) electrodes hosting [NiFeSe]hydrogenase (H2ase) and [W]-formate dehydrogenase (FDH). The enzymes used in this study have been selected for solar-driven H2 evolution or CO2-to-formate conversion because of their capability of interfacing with electrodes through a direct-electron transfer (DET) mechanism. Simulations and experiments highlight the benefit of co-immobilising the enzyme carbonic anhydrase (CA), for tuning the local chemical equilibrium and enhancing electrochemical performance. Electrochemical impedance spectroscopy (EIS) also resolves electronic signatures for each biotic-abiotic interface, revealing new insights on interfacial charge transfer mechanisms. Our approach avoids the use of external and non-innocent components such as Good's buffers or viologen-based mediators, allowing for the construction of a nature-inspired artificial leaf, driving H2 or formate production directly coupled to H2O oxidation completely powered by sunlight (Fig. ).