Trade-offs between enzyme fitness and solubility illuminated by deep mutational scanning
[1];
- Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824,
- Bioscience Division, Los Alamos National Laboratory, Los Alamos, NM 87545,
- Department of Chemical Engineering and Materials Science, Michigan State University, East Lansing, MI 48824,
- Department of Chemical Engineering and Materials Science, Michigan State University, East Lansing, MI 48824,, Department of Biosystems and Agricultural Engineering, Michigan State University, East Lansing, MI 48824
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.
- Sponsoring Organization:
- USDOE
- Grant/Contract Number:
- AC02-76SF00515
- OSTI ID:
- 1343782
- Journal Information:
- Proceedings of the National Academy of Sciences of the United States of America, Journal Name: Proceedings of the National Academy of Sciences of the United States of America Vol. 114 Journal Issue: 9; ISSN 0027-8424
- Publisher:
- Proceedings of the National Academy of SciencesCopyright Statement
- Country of Publication:
- United States
- Language:
- English
Web of Science
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