Towards the construction of high-quality mutagenesis libraries

Biotechnol Lett. 2018 Jul;40(7):1101-1107. doi: 10.1007/s10529-018-2559-7. Epub 2018 Apr 26.

Abstract

Objectives: To improve the quality of mutagenesis libraries in directed evolution strategy.

Results: In the process of library transformation, transformants which have been shown to take up more than one plasmid might constitute more than 20% of the constructed library, thereby extensively impairing the quality of the library. We propose a practical transformation method to prevent the occurrence of multiple-plasmid transformants while maintaining high transformation efficiency. A visual library model containing plasmids expressing different fluorescent proteins was used. Multiple-plasmid transformants can be reduced through optimizing plasmid DNA amount used for transformation based on the positive correlation between the occurrence frequency of multiple-plasmid transformants and the logarithmic ratio of plasmid molecules to competent cells.

Conclusions: This method provides a simple solution for a seemingly common but often neglected problem, and should be valuable for improving the quality of mutagenesis libraries to enhance the efficiency of directed evolution strategies.

Keywords: Directed evolution; Multiple-plasmid transformant; Mutagenesis library; Transformation; Transformation efficiency.

MeSH terms

  • Directed Molecular Evolution / methods*
  • Escherichia coli / genetics
  • Gene Library*
  • Plasmids / genetics
  • Transformation, Bacterial / genetics