9US2

Crystal structure of YgdH from Neisseria meningitidis

Summary for 9US2

• Entry DOI: 10.2210/pdb9us2/pdb
• Descriptor: Cytokinin riboside 5'-monophosphate phosphoribohydrolase, CITRIC ACID (3 entities in total)
• Functional Keywords: cytokinin riboside 5'-monophosphate phosphoribohydrolase with a strong preference for ump, hydrolase
• Biological source: Neisseria meningitidis
• Total number of polymer chains: 3
• Total formula weight: 68330.33

Authors

Chen, W.Q.,Yu, L.,Chen, R.Y. (deposition date: 2025-05-01, release date: 2025-08-06, Last modification date: 2025-11-12)

Primary citation

Yu, L.,Chen, R.,Zhang, C.,Wang, Z.,Wang, Z.,Zeng, X.,Liang, H.,He, Y.,She, Y.,Wang, Y.,Gong, R.,Song, X.,Deng, Z.,Fei, Q.,Chen, W.
A combined pseudouridine biomanufacturing platform enabled by a streamlined designer pathway.
Nat Commun, 16:8866-8866, 2025

PubMed 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. Moreover, a thyA-dependent, tunable, and eco-friendly strategy for sustainable Ψ production is demonstrated in a 5 L bioreactor achieving titer of 45.3 g·L. Finally, we establish a simplified-strategy for rapid Ψ purification with a recovery-rate of 71%, and techno-economic analysis is employed to validate the feasibility and advantages of this fermentation platform for Ψ biomanufacturing. Therefore, this study provides a blueprint for industrial-production of nucleoside-related molecules.

PubMed: 41053063
DOI: 10.1038/s41467-025-63906-0

Experimental method

X-RAY DIFFRACTION (1.8 Å)