Chemical Sciences Seminars

Engineering Artificial Metalloenzyme for Enantioselective Catalysis

by Dr. Poonam Srivastava (Modern Meadow Inc. New Jersey)

Thursday, August 29, 2019 from to (Asia/Kolkata)
at AG-80
Description
Artificial metalloenzymes (ArMs) offer new opportunities to improve catalytic selectivity and efficiency. They are a class of catalysts that result from incorporation of an organometallic catalyst precursor within a host protein. This combination exploits the reactivity of the transition metal catalysts while taking advantage of the selectivity and adaptability of proteins. Our research has demonstrated formation of ArMs through strain promoted azide-alkyne cycloaddition. It is a ‘click’ bioconjugation approach, where a covalent link is formed between metal complex and protein through cycloaddition of a strained alkyne linker and genetically encoded p-azidophenyl alanine on the protein scaffold. Several scaffold proteins and cofactor components were explored to demonstrate versatility of this method. Extensive biophysical characterization of these Arms was also done by mass spectrophotometry, fluorescence spectroscopy and X-ray crystallography. Scaffold proteins were engineered to get accelerated bioconjugation of metal cofactors without perturbing the structural conformation around the catalytic site. Enantioselective carbene insertion into Si-H bond and olefin has been observed using dirhodium based ArMs. Further improvement in selectivity was explored via structure based single point mutagenesis and directed protein evolution approach.