Artificial Metalloenzymes:  (Strept)avidin as Host for Enantioselective Hydrogenation by Achiral Biotinylated Rhodium−Diphosphine Complexes

We report on the generation of artificial metalloenzymes based on the noncovalent incorporation of biotinylated rhodium−diphosphine complexes in (strept)avidin as host proteins. A chemogenetic optimization procedure allows one to optimize the enantioselectivity for the reduction of acetamidoacrylic acid (up to 96% ee (<i>R</i>) in streptavidin S112G and up to 80% ee (<i>S</i>) in WT avidin). The association constant between a prototypical cationic biotinylated rhodium−diphosphine catalyst precursor and the host proteins was determined at neutral pH:  log <i>K</i>_a = 7.7 for avidin (pI = 10.4) and log <i>K</i>_a = 7.1 for streptavidin (pI = 6.4). It is shown that the optimal operating conditions for the enantioselective reduction are 5 bar at 30 °C with a 1% catalyst loading.