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http://dx.doi.org/10.25673/115434
Titel: | 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(en): | Schulz, Vladislava Galeano Nuñez, Diana Carolina ![]() Herzberg, Martin Nies, Dietrich H. |
Erscheinungsdatum: | 2024 |
Art: | Artikel |
Sprache: | Englisch |
Zusammenfassung: | 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. |
URI: | https://opendata.uni-halle.de//handle/1981185920/117388 http://dx.doi.org/10.25673/115434 |
Open-Access: | ![]() |
Nutzungslizenz: | ![]() |
Journal Titel: | Journal of bacteriology |
Verlag: | Soc. |
Verlagsort: | Washington, DC |
Band: | 206 |
Heft: | 2 |
Originalveröffentlichung: | 10.1128/jb.00395-23 |
Seitenanfang: | 1 |
Seitenende: | 28 |
Enthalten in den Sammlungen: | Open Access Publikationen der MLU |
Dateien zu dieser Ressource:
Datei | Beschreibung | Größe | Format | |
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schulz-et-al-2024-protecting-the-achilles-heel-three-fole-i-type-gtp-cyclohydrolases-needed-for-full-growth-of-metal.pdf | 5.83 MB | Adobe PDF | ![]() Öffnen/Anzeigen |