PERRC: Protease Engineering with Reactant Residence Time Control.

ABSTRACT: Proteases with engineered specificity hold great potential for targeted therapeutics, protein circuit construction, and biotechnology applications. However, many proteases exhibit broad substrate specificity, limiting their applications. Engineering protease specificity remains challenging because evolving a protease to recognize a new substrate, without counterselecting against its native substrate, often results in high residual activity on the original substrate. To address this, we developed Protease Engineering with Reactant Residence Time Control (PERRC), a platform that exploits the correlation between endoplasmic reticulum (ER) retention sequence strength and ER residence time. PERRC allows precise control over the stringency of protease evolution by adjusting counterselection to s

SUBMITTER: Nelson S 

PROVIDER: S-EPMC11908129 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature