In microbial biosynthesis, cross-species enzymes are used to reconstruct specific metabolic pathways and a large number of mutants are produced in directed evolution. The huge amount of experimental data push protein engineering to the frontiers: How to quickly integrate catalytic efficiency of massive mutants obtained from the high-throughput platform? Can we extend substrate diversity with reaction mechanism and artificial evolution?
We propose that pre-reaction state could help to figure out the chemical selectivity in enzyme engineering. Because microbes reuse functional parts of primary metabolism and deform the reaction potential surface from perfect to unperfect, a few transition states and intermediates becomes turn-over determining. It also makes pre-reaction state applicable to rationalize substrate diversity and mutation effect observed in experiments. We would introduce how to analyze the essential pre-reaction state with molecular dynamics and QM/MM method.
Dr. Zhao’s research focuses on the reaction mechanisms of biosynthetic and industrial enzymes, DNA chemical modifications, and protein post-translational modifications. After completing his undergraduate studies at University of Science and Technology of China, he attended the Key State Laboratory of Rare Earth Materials Chemistry and Applications and obtained his M.Sc. from Peking University. Then he moved to computational chemistry under Prof. Yundong Wu’s mentorship and received his Ph.D. from the Hong Kong University of Science and Technology in 2002. He joined Prof. Kendall N. Houk’s group at University of California, Los Angeles, and then worked at Physical and Chemical Properties Division on a PM-USA fellowship at National Institute of Standards and Technology, Maryland, USA. Zhao returned to China and joined Shanghai Jiao Tong University as a full professor in 2009. He has received awards that include UCLA Excellent Postdoctor, Pujiang Talent, Shanghai Oriental Scholar, and MOE New-Century Excellent Talent.
Seminar Series by the NYU-ECNU Center for Computational Chemistry at NYU Shanghai