Towards the Evolution of Artificial Metalloenzymes—A Protein Engineer's Perspective

Evolution revolution: In the past, incorporating artificial cofactors into proteins hampered high‐throughput approaches for the directed evolution of biohybrid catalysts. This Minireview provides an overview of the challenges, approaches, and success stories in the directed evolution of biohybrid catalysts and their transformation into highly specialized and enantioselective artificial metalloenzymes.

Abstract

Incorporating artificial metal‐cofactors into protein scaffolds results in a new class of catalysts, termed biohybrid catalysts or artificial metalloenzymes. Biohybrid catalysts can be modified chemically at the first coordination sphere of the metal complex, as well as at the second coordination sphere provided by the protein scaffold. Protein‐scaffold reengineering by directed evolution exploits the full power of nature's diversity, but requires validated screening and sophisticated metal cofactor conjugation to evolve biohybrid catalysts. In this Minireview, we summarize the recent efforts in this field to establish high‐throughput screening methods for biohybrid catalysts and we show how non‐chiral catalysts catalyze reactions enantioselectively by highlighting the first successes in this emerging field. Furthermore, we shed light on the potential of this field and challenges that need to be overcome to advance from biohybrid catalysts to true artificial metalloenzymes.

from A via a.sfakia on Inoreader http://bit.ly/2SqUfzs