Bacterial Glutamine Synthetases as a Novel Metabolic Selection Marker to Improve CHO Cell Culture Performance Through Selection Stringency Modulation.

ABSTRACT: The use of metabolic selection markers has advanced stable cell line generation, increasing productivity while simultaneously eliminating the need for antibiotic reagents. This study explores the potential of bacterially derived glutamine synthetases (GS) as a novel generation of metabolic selection markers to further enhance CHO cell culture performance. GS-I proteins were extracted from the genomes of enterobacterial and actinomycetes species. Three of these enzymes demonstrated functionality when stably transfected into GS-deficient CHO cells, leading to a 3- to 4-fold increase in antibody titer compared to endogenous GS from Cricetulus griseus. This study indicates that the functionality of bacterial GS enzymes in mammalian cells is determined by solvent accessibility and the geometry

SUBMITTER: Heinzelmann D 

PROVIDER: S-EPMC12415323 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature