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Journal Club | Directed evolution of enzymes: move the evolution process into laboratories (2018 Noble Prize in Chemistry)

Mar.24.2019

Speaker:Aoyue Mao(茅傲岳)Peiwen Yang(杨培文)Ruoxuan Zhuang(庄若璇)Qijia Wei(魏琦佳)

Time:10:00 - 13:00

Location:Room 348, Wangkezhen Building

Abstract:


Natural evolution of enzymes has existed since the emergence of life on Earth. Genes have mutated and proteins have evolved to improve the fitness of an organism. Directed evolution, which moves the evolution process into the laboratory and speeds it up, contains iterative rounds of mutagenesis, selection, and amplification. It was advanced by Prof. Frances Arnold and earned her the 2018 Noble Prize in Chemistry. Directed evolution of enzymes leads to the discovery of new reactivity, transformation not known in biology, and even reactivity hard to achieve by small-molecule catalysts, like the production of highly strained cyclopropene (环丙烯) and bicyclobutanes and the synthesis of Chiral Organoborane. Directed evolution has also been widely used to improve protein stability for use at harsh conditions, Improve binding affinity of therapeutic antibodies and alter substrate specificity of existing enzymes like evolving aminoacyl-tRNA synthetase to specifically accept unnatural amino acid. For the directed evolution, a single round of mutation, gene expression, screening or selection, and replication typically requires days or longer. Several years ago, Prof. David Liu’s group developed phage-assisted continuous evolution (PACE), which employs bacteriophage to do the directed evolution, can make dozens of rounds of evolution occurring in a single day without human intervention, dramatically speeding up the laboratory evolution process. So far, PACE has been used to evolve many kinds of proteins like polymerase, protease, genome modification enzymes and so on. Due to the rapid speed of evolution, PACE is also used to answer some basic questions in evolutionary biology.





Guest information:

1. Dr. Chong Zhang (THU)

http://www.cssb.tsinghua.edu.cn/zh/core-staff/item/159-2015-10-26-15-59-08




Recommend Literatures:
Review:

1. Arnold, Frances H. "Directed evolution: bringing new chemistry to life." Angewandte Chemie International Edition 57.16 (2018): 4143-4148.

Link: https://doi.org/10.1002/anie.201708408

2. Packer, Michael S., and David R. Liu. "Methods for the directed evolution of proteins." Nature Reviews Genetics 16.7 (2015): 379.

Link: https://www.nature.com/articles/nrg3927

Papers:
1. Kan, SB Jennifer, et al. "Genetically programmed chiral organoborane synthesis." Nature 552.7683 (2017): 132.
Link: https://www.nature.com/articles/nature24996

2. Esvelt, Kevin M., Jacob C. Carlson, and David R. Liu. "A system for the continuous directed evolution of biomolecules." Nature 472.7344 (2011): 499.

Link: https://www.nature.com/articles/nature09929