Characterization and Crystal Structure Elucidation of the l-Homoserine O-Succinyltransferase MetXS From Cupriavidus necator H16.
- 1Department of Chemical and Pharmaceutical Biology, Groningen Research Institute of Pharmacy, University of Groningen, Groningen, The Netherlands.
- 2iAMB - Institute of Applied Microbiology, RWTH Aachen University, Aachen, Germany.
Abstract
Among the promising microbial platforms to produce value-added products from CO₂, chemolithoautotrophic bacteria, such as Cupriavidus necator H16 (C. necator), stand out due to their ability to fix CO₂ via the Calvin-Benson-Bassham (CBB) cycle. Although C. necator has been extensively studied as a biotechnological production host, several of its biosynthetic pathways remain incompletely characterized at the biochemical level. This includes l-methionine biosynthesis, for which genome-based functional annotations of key enzymes have not been validated experimentally. In this study, we identified and characterized CnMetXS, a homoserine O-succinyltransferase involved in l-methionine biosynthesis in C. necator. Biochemical characterization demonstrated that CnMetXS catalyzes the transsuccinylation of l-homoserine to O-succinyl-l-homoserine but exhibits no transacetylase activity. Additionally, we determined the apo crystal structure of CnMetXS at 1.86 Å resolution, revealing a homodimer with a MetX-G2 active-site architecture and distinct conformations of the active-site lid region. Structural analysis and docking suggest that Arg335 stabilizes the succinylated enzyme intermediate and explains the observed succinyl-CoA specificity. Together, these results establish the function of CnMetXS and pave the way for metabolic engineering strategies to produce l-methionine in C. necator.
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BibTeX
@article{meier2026characterization,
title = {{Characterization and Crystal Structure Elucidation of the l-Homoserine O-Succinyltransferase MetXS From Cupriavidus necator H16.}},
author = {Hannah Pia Franziska Meier and Rick Oerlemans and Henrik Terholsen and Matthew R Groves and Lars Lauterbach and Sandy Schmidt},
journal = {Chembiochem : a European journal of chemical biology},
year = {2026},
month = oct,
doi = {10.1002/cbic.70564},
url = {https://europepmc.org/article/MED/42902934},
note = {CC BY},
}
RIS
TY - JOUR
TI - Characterization and Crystal Structure Elucidation of the l-Homoserine O-Succinyltransferase MetXS From Cupriavidus necator H16.
AU - Hannah Pia Franziska Meier
AU - Rick Oerlemans
AU - Henrik Terholsen
AU - Matthew R Groves
AU - Lars Lauterbach
AU - Sandy Schmidt
PY - 2026
DA - 2026/10/01
JO - Chembiochem : a European journal of chemical biology
DO - 10.1002/cbic.70564
UR - https://europepmc.org/article/MED/42902934
AB - Among the promising microbial platforms to produce value-added products from CO₂, chemolithoautotrophic bacteria, such as Cupriavidus necator H16 (C. necator), stand out due to their ability to fix CO₂ via the Calvin-Benson-Bassham (CBB) cycle. Although C. necator has been extensively studied as a biotechnological production host, several of its biosynthetic pathways remain incompletely characterized at the biochemical level. This includes l-methionine biosynthesis, for which genome-based functional annotations of key enzymes have not been validated experimentally. In this study, we identified and characterized CnMetXS, a homoserine O-succinyltransferase involved in l-methionine biosynthesis in C. necator. Biochemical characterization demonstrated that CnMetXS catalyzes the transsuccinylation of l-homoserine to O-succinyl-l-homoserine but exhibits no transacetylase activity. Additionally, we determined the apo crystal structure of CnMetXS at 1.86 Å resolution, revealing a homodimer with a MetX-G2 active-site architecture and distinct conformations of the active-site lid region. Structural analysis and docking suggest that Arg335 stabilizes the succinylated enzyme intermediate and explains the observed succinyl-CoA specificity. Together, these results establish the function of CnMetXS and pave the way for metabolic engineering strategies to produce l-methionine in C. necator.
SN - 1439-4227
SN - 1439-7633
ER -