CO reduction has drawn increasing attention owing to the concern of global warming. Water splitting-biosynthetic hybrid systems are novel and efficient approaches for CO conversion. Intimate coupling of electrocatalysts and biosynthesis requires the catalysts possess both high catalytic performance and excellent biocompatibility, which is a bottleneck of developing such catalysts. Here, a complex of Ni nanoparticles embedded in N-doped carbon nanotubes (Ni@N-C) is synthesized as a hydrogen evolution reaction electrocatalyst and is coupled with a hydrogen oxidizing autotroph, Cupriavidus necator H16, to convert CO to poly-β-hydroxybutyrate. In Ni@N-C, the Ni nanoparticles are encapsulated in N-C nanotubes, which prevents bacteria from direct contact with Ni and inhibits Ni leaching. As a result, Ni@N-C exhibits excellent biocompatibility and stability. This work demonstrates that electrocatalysts and biosynthesis can be intimately coupled through rational catalyst design.