Discovery of highly active kynureninases for cancer immunotherapy through protein language model.

ABSTRACT: Tailor-made enzymes empower a wide range of versatile applications, although searching for the desirable enzymes often requires high throughput screening and thus poses significant challenges. In this study, we employed homology searches and protein language models to discover and prioritize enzymes by their kinetic parameters. We aimed to discover kynureninases as a potentially versatile therapeutic enzyme, which hydrolyses L-kynurenine, a potent immunosuppressive metabolite, to overcome the immunosuppressive tumor microenvironment in anticancer therapy. Subsequently, we experimentally validated the efficacy of four top-ranked kynureninases under in vitro and in vivo conditions. Our findings revealed a catalytically most active one with a nearly twofold increase in turnover number over th

SUBMITTER: Eom H 

PROVIDER: S-EPMC11704957 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature