Work

Characterization and Crystal Structure Elucidation of the l ‐Homoserine O ‐Succinyltransferase MetXS From Cupriavidus necator H16

Year: 2026

Type: article

Abstract: 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.

Source: ChemBioChem

DOI: 10.1002/cbic.70564

Authors: Hannah Pia Franziska Meier, Rick Oerlemans, Henrik Terholsen, Matthew R. Groves, Lars Lauterbach, Sandy Schmidt

Institutions: University of Groningen, RWTH Aachen University

Language: English

Topic: Enzyme Structure and Function

Subfield: Structural Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: hybrid

Estimated APC paid: $4,430