Computer‐Assisted Recombination (CompassR) Teaches us How to Recombine Beneficial Substitutions from Directed Evolution Campaigns
A main remaining challenge in protein engineering is how to recombine beneficial substitutions. Systematic recombination studies show that poorly performing variants are usually obtained after recombination of 3 to 4 beneficial substitutions. This limits researchers in exploiting nature's poten...
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| Veröffentlicht in: | Chemistry : a European journal 2020-01, Vol.26 (3), p.643-649 |
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| creator | Cui, Haiyang Cao, Hao Cai, Haiying Jaeger, Karl‐Erich Davari, Mehdi D. Schwaneberg, Ulrich |
| description | A main remaining challenge in protein engineering is how to recombine beneficial substitutions. Systematic recombination studies show that poorly performing variants are usually obtained after recombination of 3 to 4 beneficial substitutions. This limits researchers in exploiting nature's potential in generating better enzymes. The Computer‐assisted Recombination (CompassR) strategy provides a selection guide for beneficial substitutions that can be recombined to gradually improve enzyme performance by analysis of the relative free energy of folding (ΔΔGfold). The performance of CompassR was evaluated by analysis of 84 recombinants located on 13 positions of Bacillus subtilis lipase A. The finally obtained variant F17S/V54K/D64N/D91E had a 2.7‐fold improved specific activity in 18.3 % (v/v) 1‐butyl‐3‐methylimidazolium chloride ([BMIM][Cl]). In essence, the deducted CompassR rule allows recombination of beneficial substitutions in an iterative manner and empowers researchers to generate better enzymes in a time‐efficient manner.
True North: The Computer‐assisted Recombination (CompassR) strategy provides a selection guide for beneficial substitutions that can be recombined to gradually improve enzyme performance by analysis of the relative free energy of folding (ΔΔGfold). |
| doi_str_mv | 10.1002/chem.201903994 |
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| subjects | Bacillus subtilis lipase A Chemistry Directed evolution Enzymes foldX Free energy Iterative methods Lipase Performance evaluation Protein engineering Recombinants Recombination Researchers |
| title | Computer‐Assisted Recombination (CompassR) Teaches us How to Recombine Beneficial Substitutions from Directed Evolution Campaigns |
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