Characterization of a spiramycin-inactivating macrolide esterase
- 1University of Saskatchewan
Abstract
Recent functional annotation of /{beta}-hydrolases as macrolide esterases has the opened door to genome mining efforts exploring the sequencing diversity of the family. Nevertheless, unexplained resistance phenotypes associated with these enzymes remain in the literature. Inspired by a report of macrolide-resistant Streptococcus uberis(1), we have annotated and characterized an enzyme named EstS as a macrolide esterase. Curiously, phylogenetic analyses revealed that EstS is most often encoded by Escherichia coli, including human and animal pathogens, rather than Gram-positive organisms. Although EstS could hydrolyze a series of macrolides, heterologous expression of estS conferred protection against only the natural products spiramycin and tylosin. Steady-state kinetic analyses by isothermal titration calorimetry and high-performance chromatography coupled to mass spectrometry revealed that EstS prefers spiramycin as a substrate consistent with higher protection observed in E. coli.
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BibTeX
@misc{myziuk2026characterization,
title = {{Characterization of a spiramycin-inactivating macrolide esterase}},
author = {I. Myziuk and Z. Mulla and T. Jannat and A. Ruzzini},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.26.761979},
url = {https://www.biorxiv.org/content/10.64898/2026.10.26.761979v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Characterization of a spiramycin-inactivating macrolide esterase
AU - I. Myziuk
AU - Z. Mulla
AU - T. Jannat
AU - A. Ruzzini
PY - 2026
DA - 2026/10/26
PB - bioRxiv
DO - 10.64898/2026.10.26.761979
UR - https://www.biorxiv.org/content/10.64898/2026.10.26.761979v1
AB - Recent functional annotation of /{beta}-hydrolases as macrolide esterases has the opened door to genome mining efforts exploring the sequencing diversity of the family. Nevertheless, unexplained resistance phenotypes associated with these enzymes remain in the literature. Inspired by a report of macrolide-resistant Streptococcus uberis(1), we have annotated and characterized an enzyme named EstS as a macrolide esterase. Curiously, phylogenetic analyses revealed that EstS is most often encoded by Escherichia coli, including human and animal pathogens, rather than Gram-positive organisms. Although EstS could hydrolyze a series of macrolides, heterologous expression of estS conferred protection against only the natural products spiramycin and tylosin. Steady-state kinetic analyses by isothermal titration calorimetry and high-performance chromatography coupled to mass spectrometry revealed that EstS prefers spiramycin as a substrate consistent with higher protection observed in E. coli.
ER -