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Publication Abstract from PubMed

3-Hexulose-6-phosphate synthase, a key enzyme in the ribulose monophosphate pathway, plays a central role in formaldehyde assimilation and detoxification, offering great potential for third-generation green biomanufacturing. In this study, we determined the crystal structure of HPS from Pyrococcus horikoshii at a 2.64 A resolution. Combined approaches, including molecular docking, multiple sequence alignment, and alanine scanning, identified critical catalytic residues. Two variants, T136C and V186W, exhibited over 6-fold higher activity than the wild type. Molecular dynamics simulations indicated increased structural rigidity and enhanced stability upon substrate (d-ribulose-5-phosphate) binding, along with significantly improved binding energies. Furthermore, an enzyme cascade converting d-xylose and formaldehyde to d-fructose-6-phosphate was constructed to evaluate the HPS activity under optimized conditions. These findings provide insights into the catalytic mechanism of HPS and offer a basis for its application in one-carbon bioconversion.

Crystal Structure, Mutations, and Catalytic Properties of 3-Hexulose-6-phosphate Synthase from Pyrococcus horikoshii.,Li Y, Liu Y, Ji Y, Xu H, Wang H, Feng Y, Liu L J Agric Food Chem. 2025 Jul 9;73(27):17103-17113. doi: 10.1021/acs.jafc.5c02365. , Epub 2025 Jun 28. PMID:40580126^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.