Details zur Publikation

Kategorie Textpublikation
Referenztyp Zeitschriften
DOI 10.1128/jb.00395-23
Lizenz creative commons licence
Titel (primär) Protecting the Achilles heel: three FolE_I-type GTP-cyclohydrolases needed for full growth of metal-resistant Cupriavidus metallidurans under a variety of conditions
Autor Schulz, V.; Galea, D.; Herzberg, M. ORCID logo ; Nies, D.H.
Quelle Journal of Bacteriology
Erscheinungsjahr 2024
Department EAC
Band/Volume 206
Heft 2
Seite von e00395-23
Sprache englisch
Topic T9 Healthy Planet
Supplements https://journals.asm.org/doi/suppl/10.1128/jb.00395-23/suppl_file/jb.00395-23-s0001.pdf
Keywords folate biosynthesis; zinc; ZMP
Abstract In Cupriavidus metallidurans and other bacteria, biosynthesis of the essential biochemical cofactor tetrahydrofolate (THF) initiates from guanosine triphosphate (GTP). This step is catalyzed by FolE_I-type GTP cyclohydrolases, which are either zinc-dependent FolE_IA-type or metal-promiscuous FolE_IB-type enzymes. As THF is also essential for GTP biosynthesis, GTP and THF synthesis form a cooperative cycle, which may be influenced by the cellular homeostasis of zinc and other metal cations. Metal-resistant C. metallidurans harbors one FolE_IA-type and two FolE_IB-type enzymes. All three proteins were produced in Escherichia coli. FolE_IA was indeed zinc dependent and the two FolE_IB enzymes metal-promiscuous GTP cyclohydrolases in vitro, the latter, for example, functioning with iron, manganese, or cobalt. Single and double mutants of C. metallidurans with deletions in the folE_I genes were constructed to analyze the contribution of the individual FolE_I-type enzymes under various conditions. FolE_IA was required in the presence of cadmium, hydrogen peroxide, metal chelators, and under general metal starvation conditions. FolE_IB1 was important when zinc uptake was impaired in cells without the zinc importer ZupT (ZIP family) and in the presence of trimethoprim, an inhibitor of THF biosynthesis. FolE_IB2 was needed under conditions of low zinc and cobalt but high magnesium availability. Together, these data demonstrate that C. metallidurans requires all three enzymes to allow efficient growth under a variety of conditions.
dauerhafte UFZ-Verlinkung https://www.ufz.de/index.php?en=20939&ufzPublicationIdentifier=28709
Schulz, V., Galea, D., Herzberg, M., Nies, D.H. (2024):
Protecting the Achilles heel: three FolE_I-type GTP-cyclohydrolases needed for full growth of metal-resistant Cupriavidus metallidurans under a variety of conditions
J. Bacteriol. 206 (2), e00395-23 10.1128/jb.00395-23