Chemogenetic protein engineering: an efficient tool for the optimization of artificial metalloenzymes.
Artificial metalloenzymes, based on the incorporation of a catalytically active organometallic moiety within a host protein, lie at the interface between organometallic and enzymatic catalysis. In terms of activity, reaction repertoire, substrate range and operating conditions, they take advantage of the versatility of the organometallic chemistry. In contrast, the enantioselectivity is determined by the biomolecular scaffold, which provides a well defined second coordination sphere to the organometallic moiety, reminiscent of enzymes. The attractive feature of such systems is their optimization potential, which combines chemical and genetic methods (i.e. chemogenetic) to screen diversity space. This feature article describes the implementation of such an optimization protocol for artificial transfer hydrogenases, for which we have the most detailed understanding.
Pordea
Anca
A
Institute of Chemistry, University of Neuchâtel, Avenue Bellevaux 51, CP158, CH-2009 Neuchâtel, Switzerland. thomas.ward@unine.ch
Ward
Thomas R
TR
D001665:Binding Sites; D002384:Catalysis; D018360:Crystallography, X-Ray; D006864:Hydrogenase / Q000737:chemistry* / Q000235:genetics; D008024:Ligands; D008667:Metalloproteins / Q000737:chemistry* / Q000235:genetics; D008958:Models, Molecular; D008968:Molecular Conformation; D015202:Protein Engineering / Q000379:methods*; D012428:Ruthenium / Q000737:chemistry*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013379:Substrate Specificity / Q000235:genetics
D008024:Ligands; D008667:Metalloproteins; D012428:Ruthenium; D006864:Hydrogenase