Enabling Protein-Hosted Organocatalytic TransformationsReview
In this review, the development of organocatalytic artificial enzymes will be discussed. This area of protein engineering research has underlying importance, as it enhances the biocompatibility of organocatalysis for applications in chemical and synthetic biology research whilst expanding the catalytic repertoire of enzymes. The approaches towards the preparation of organocatalytic artificial enzymes, techniques used to improve their performance (selectivity and reactivity) as well as examples of their applications are presented. Challenges and opportunities are also discussed.
Transfer Hydrogenations Catalyzed by Streptavidin-Hosted Secondary Amine Organocatalysts
Here, the streptavidin–biotin technology was applied to enable organocatalytic transfer hydrogenation. By introducing a biotin-tethered pyrrolidine (1) to the tetrameric streptavidin (T-Sav), the resulting hybrid catalyst was able to mediate hydride transfer from dihydro-benzylnicotinamide (BNAH) to α,β-unsaturated aldehydes. Hydrogenation of cinnamaldehyde and some of its aryl-substituted analogues was found to be nearly quantitative. Kinetic measurements revealed that the T-Sav:1 assembly possesses enzyme-like behavior, whereas isotope effect analysis, performed by QM/MM simulations, illustrated that the step of hydride transfer is at least partially rate-limiting. These results have proven the concept that T-Sav can be used to host secondary amine-catalyzed transfer hydrogenations.
Metal: ---Ligand type: Biotinylated pyrrolidineHost protein: Streptavidin (Sav)Anchoring strategy: SupramolecularOptimization: ---Notes: Maximum conversion is 95%; Efficiency of hydride transfer is largely affected by electrostatic properties of the para substituents of the aromatic a,b-unsaturated aldehyde substrate (cinnamaldehyde)