Building tailor-made bioenergetic proteins and circuits from de novo redox proteins

Natural electron-conducting circuits play essential roles in respiration and photosynthesis and are therefore of fundamental importance to all life on earth. These circuits are composed of redox-active cofactors housed within proteins, or multi-subunit protein complexes, facilitating the conduction of electrons in support of transmembrane proton pumping, redox catalysis and the extracellular delivery of electrons to terminal electron acceptors. Though the natural electron-conducting circuitry can be complex, it is possible to recapitulate selected, desirable functions within minimalist de novo-designed proteins. Here we highlight recent advances in the de novo design of redox proteins and enzymes that illustrate the progress and potential of this approach, providing insight into the workings and engineering of their natural counterparts, while creating a readily adaptable and robust set of components for future bioelectronic engineering.