Abstract
The salicylate synthase (YbtS) of Yersinia pestis catalyzes the initial step in the biosynthesis of yersiniabactin, an iron-scavenging siderophore and critical virulence factor. While YbtS is proposed to share a reaction mechanism with other anthranilate synthase homologs, the exact catalytic pathway has remained unresolved. In this work, stable isotope (18O) labeling and mass spectrometry are utilized to clarify the catalytic mechanism of YbtS. The results of the following set of experiments demonstrate that the salicylate hydroxyl group does not originate from solvent water, directly challenging previously proposed models. Instead, the lack of solvent-labeled oxygen incorporation and the absence of an isotope effect support a mechanism involving an internally conserved intramolecular hydroxyl group transfer from the C4 position of chorismate. These findings refine the current molecular understanding of siderophore-mediated iron acquisition in highly virulent, multidrug-resistant pathogens that acquire the Yersinia high-pathogenicity island.
Acknowledgements
The authors would like to thank Dr. Jacqueline Fetherston and Dr. Robert Perry for providing the pYbtS-H6 plasmid for efficient overexpression of YbtS. This work was supported by Public Health Service grant AI33481 to ED, JDF, and RDP.
Recommended Citation
Miller, Clarke
(2026)
"Enzymatic synthesis of salicylate in Yersina pestis proceeds via intramolecular hydroxyl group transfer.,"
Georgia Journal of Science, Vol. 84, No. 2, Article 3.
Available at:
https://journal.georgiaacademyofscience.org/gjs/vol84/iss2/3