Trade-offs between enzyme fitness and solubility illuminated by deep mutational scanning.

ABSTRACT: Proteins are marginally stable, and an understanding of the sequence determinants for improved protein solubility is highly desired. For enzymes, it is well known that many mutations that increase protein solubility decrease catalytic activity. These competing effects frustrate efforts to design and engineer stable, active enzymes without laborious high-throughput activity screens. To address the trade-off between enzyme solubility and activity, we performed deep mutational scanning using two different screens/selections that purport to gauge protein solubility for two full-length enzymes. We assayed a TEM-1 beta-lactamase variant and levoglucosan kinase (LGK) using yeast surface display (YSD) screening and a twin-arginine translocation pathway selection. We then compared these scans with

SUBMITTER: Klesmith JR 

PROVIDER: S-EPMC5338495 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature