Biotinylated Rh(III) Complexes in Engineered Streptavidin for Accelerated Asymmetric C-H Activation

• Published in: Science (American Association for the Advancement of Science) Vol. 338; no. 6106; pp. 500 - 503
• Main Authors: Hyster, Todd K., Knörr, Livia, Ward, Thomas R., Rovis, Tomislav
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 26.10.2012; The American Association for the Advancement of Science
• Subjects: Acetates; Activation; Active sites; Alkenes; Alkenes - chemistry; Aluminum; Asymmetry; Bacterial proteins; Basic amino acids; Benzamides; Benzamides - chemistry; Biochemistry; Biotinylation; Carbon - chemistry; Carboxylates; Catalysis; Catalysts; Catalytic Domain; Chemistry; Coordination Complexes - chemistry; Derivatives; Enzyme Activation; Enzymes; Enzymes - chemistry; Exact sciences and technology; General and physical chemistry; Hydrogen - chemistry; Hydrogen bonds; Mutagenesis, Site-Directed; Olefins; Protein Engineering; Rendering; Rhodium; Rhodium - chemistry; Streptavidin - chemistry; Streptavidin - genetics; Substrate Specificity; Theory of reactions, general kinetics. Catalysis. Nomenclature, chemical documentation, computer chemistry; Glutamic acid; Rhodium complex; Rhodium III; Transition element complexes; Isoquinoline derivatives; Enzyme; Organic ligand; Biotin; Metalloenzyme; Asymmetric catalysis; Protein; Homogeneous catalysis; Streptavidin; Benzenic compound; Benzamide derivatives; Aspartic acid; Organic amide; Platinoid Complexes; Ethylenic compound
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1226132

Enzymes provide an exquisitely tailored chiral environment to foster high catalytic activities and selectivities, but their native structures are optimized for very specific biochemical transformations. Designing a protein to accommodate a non-native transition metal complex can broaden the scope of enzymatic transformations while raising the activity and selectivity of small-molecule catalysis. Here, we report the creation of a bifunctional artificial metalloenzyme in which a glutamic acid or aspartic acid residue engineered into streptavidin acts in concert with a docked biotinylated rhodium(III) complex to enable catalytic asymmetric carbon-hydrogen (C-H) activation. The coupling of benzamides and alkenes to access dihydroisoquinolones proceeds with up to nearly a 100-fold rate acceleration compared with the activity of the isolated rhodium complex and enantiomeric ratios as high as 93:7.