Efficient molecular evolution to generate enantioselective enzymes using a dual-channel microfluidic droplet screening platform

Fuqiang Ma, Meng Ting Chung, Yuan Yao, Robert Nidetz, Lap Man Lee, Allen P. Liu, Yan Feng, Katsuo Kurabayashi () and Guang-Yu Yang ()
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Fuqiang Ma: Shanghai Jiao Tong University
Meng Ting Chung: University of Michigan
Yuan Yao: Harbin Institute of Technology
Robert Nidetz: University of Michigan
Lap Man Lee: University of Michigan
Allen P. Liu: University of Michigan
Yan Feng: Shanghai Jiao Tong University
Katsuo Kurabayashi: University of Michigan
Guang-Yu Yang: Shanghai Jiao Tong University

Nature Communications, 2018, vol. 9, issue 1, 1-8

Abstract: Abstract Directed evolution has long been a key strategy to generate enzymes with desired properties like high selectivity, but experimental barriers and analytical costs of screening enormous mutant libraries have limited such efforts. Here, we describe an ultrahigh-throughput dual-channel microfluidic droplet screening system that can be used to screen up to ~107 enzyme variants per day. As an example case, we use the system to engineer the enantioselectivity of an esterase to preferentially produce desired enantiomers of profens, an important class of anti-inflammatory drugs. Using two types of screening working modes over the course of five rounds of directed evolution, we identify (from among 5 million mutants) a variant with 700-fold improved enantioselectivity for the desired (S)-profens. We thus demonstrate that this screening platform can be used to rapidly generate enzymes with desired enzymatic properties like enantiospecificity, chemospecificity, and regiospecificity.

Date: 2018
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DOI: 10.1038/s41467-018-03492-6

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