Publication Details |
| Category | Text Publication |
| Reference Category | Journals |
| DOI | 10.1128/jb.00395-23 |
Licence  |
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| Title (Primary) | Protecting the Achilles heel: three FolE_I-type GTP-cyclohydrolases needed for full growth of metal-resistant Cupriavidus metallidurans under a variety of conditions |
| Author | Schulz, V.; Galea, D.; Herzberg, M.
; Nies, D.H. |
| Source Titel | Journal of Bacteriology |
| Year | 2024 |
| Department | EAC |
| Volume | 206 |
| Issue | 2 |
| Page From | e00395-23 |
| Language | 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. |
| Persistent UFZ Identifier | 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 |
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