Toward manmade light- and redox- driven oxidoreductases working in cells

Bringing the idea of integrating manmade oxidoreductases and allied proteins into cell and organelle to replace or augment component parts of metabolic and bioenergetic machinery, has some way to go to before benefit to mankind can be expected. Nevertheless, once realized, the impact on solar energy conversion into chemical fuels, on remediating hemorrhagic traumas, or on correcting respiratory dysfunction of genetic or aging origins will be considerable.

We combine first-principles light- and oxidant/reductant substrate-driven electron transfer engineering common to natural oxidoreductase proteins with first-principles α-helical protein design to reproduce oxidoreductase and related functions in structurally transparent man-made proteins we call maquettes.

Maquettes promote diverse natural functions including light-capture and multistep energy transfer and efficient charge-separation, diffusive inter-protein electron-transfer, and O2 ligation and transport. Maquettes prove to be biocompatible: bacterial expression is coupled with biogenesis and ligation of cofactors such as hemes B and C, bilins and indications of chlorophyll. Maquettes can be equipped for transported across membranes by Tat or Sec.

Recent advances in translating photosynthetic charge-separating engineering, normally considered restricted to membranes, into environments typical of water-soluble proteins greatly simplifies design and assembly of solar energy conversion in aqueous media that is more amenable to cellular expression and function. Acquisition of high-resolution crystal structures of maquettes ligating multiple different cofactors familiar in photosynthesis ad respiration is increasing design transparency.