Trade-offs between enzyme fitness and solubility illuminated by deep mutational scanning Journal Article uri icon



  • Significance; Enzymes find utility as therapeutics and for the production of specialty chemicals. Changing the amino acid sequence of an enzyme can increase solubility, but many such mutations disrupt catalytic activity. To evaluate this trade-off, we developed an experimental system to evaluate the relative solubility for nearly all possible single point mutants for two model enzymes. We find that the tendency for a given solubility-enhancing mutation to disrupt catalytic activity depends, among other factors, on how far the position is from the catalytic active site and whether that mutation has been sampled during evolution. We develop predictive models to identify mutations that enhance solubility without disrupting activity with an accuracy of 90%. These results have biotechnological applications.

publication date

  • February 28, 2017

has restriction

  • bronze

Date in CU Experts

  • September 24, 2019 4:33 AM

Full Author List

  • Klesmith JR; Bacik J-P; Wrenbeck EE; Michalczyk R; Whitehead TA

author count

  • 5

Other Profiles

International Standard Serial Number (ISSN)

  • 0027-8424

Electronic International Standard Serial Number (EISSN)

  • 1091-6490

Additional Document Info

start page

  • 2265

end page

  • 2270


  • 114


  • 9