A combined pseudouridine biomanufacturing platform enabled by a streamlined designer pathway.

ABSTRACT: mRNA vaccines, featured by incorporated pseudouridine (Ψ), represent a milestone in combating diseases, thus highlighting Ψ importance in drug development. However, economic and environmental challenges have persisted in sustainable Ψ production. Here, we formulate a streamlined designer Ψ pathway, comprising UMP nucleosidase, ΨMP glycosidase, and ΨMP phosphatase, and realize its gram-scale production by targeted discovery of a prominent UMP-preferred nucleosidase (NmYgdH). The optimized pathway, containing NmYgdH, RjPsuG (ΨMP glycosidase), and HDHD1 (ΨMP-specific phosphatase) is cloned into E. coli and systematic evaluation of multiple strategies achieves a Ψ titer of 44.8 g·L^-1. Moreover, a thyA-dependent, tunable, and eco-friendly strategy for sustainable Ψ production is demo

SUBMITTER: Yu L 

PROVIDER: S-EPMC12500856 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature