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The ancient alarmone ZTP and zinc homeostasis in Bacillus subtilis
Author(s) -
Nies Dietrich H.
Publication year - 2019
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.14332
Subject(s) - bacillus subtilis , zinc , biology , biochemistry , riboswitch , enzyme , nucleoside triphosphate , biosynthesis , gtp' , chaperone (clinical) , rna , nucleotide , chemistry , bacteria , gene , genetics , non coding rna , organic chemistry , medicine , pathology
Summary In Bacillus subtilis a sophisticated regulatory circuit that involves Z nucleoside triphosphate (ZTP) is recruited to optimize cellular zinc distribution when cytoplasmic zinc is scarce. This process uses enzymatic reactions to measure the pool of available zinc ions and amplifies this signal to control the activity of zinc chaperones. The ZTP‐dependent regulatory circuit that is exploited for zinc homeostasis controls purine and folate biosynthesis, which starts with GTP as initial substrate. Low concentrations of formyl‐tetrahydrofolate (fTHF) lead to accumulation of the intermediate 5′‐phosphoribosyl‐4‐carboxyamide‐5‐aminoimidazole (AICAR or ZMP), which is pyrophosphorylated by another intermediate to ZTP. This alarmone activates expression of genes using a ZTP‐dependent riboswitch in many bacterial strains. In this way, the cellular folate concentration controls folate biosynthesis via the enzymatic activity of the fTHF‐dependent AICAR‐transforming reaction. Zinc distribution control is layered onto this circuit. The ‘sensor’ is the activity of the initial reaction of folate synthesis from GTP, which is catalyzed by a zinc‐dependent enzyme FolE IA or its metal‐cambialistic paralog FolE IB . Consequently, low zinc lowers folate levels, causing AICAR accumulation and ZTP formation. In addition to the riboswitch, ZTP activates the zinc chaperone ZagA of the COG0523 protein family, which efficiently allocate zinc to zinc‐dependent enzymes such as FolE IA .