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An alternative pathway for reduced folate biosynthesis in bacteria and halophilic archaea
Author(s) -
Levin Itay,
Giladi Moshe,
AltmanPrice Neta,
Ortenberg Ron,
Mevarech Moshe
Publication year - 2004
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/j.1365-2958.2004.04339.x
Subject(s) - biology , dihydropteroate synthase , haloferax volcanii , dihydrofolate reductase , biochemistry , escherichia coli , dhps , atp synthase , gene , microbiology and biotechnology , archaea , plasmodium falciparum , pyrimethamine , malaria , immunology
Summary Whereas tetrahydrofolate is an essential cofactor in all bacteria, the gene that encodes the enzyme dihydrofolate reductase (DHFR) could not be identified in many of the bacteria whose genomes have been entirely sequenced. In this communication we show that the halophilic archaea Halobacterium salinarum and Haloarcula marismortui contain genes coding for proteins with an N‐terminal domain homologous to dihydrofolate synthase (FolC) and a C‐terminal domain homologous to dihydropteroate synthase (FolP). These genes are able to complement a Haloferax volcanii mutant that lacks DHFR. We also show that the Helicobacter pylori dihydropteroate synthase can complement an Escherichia coli mutant that lacks DHFR. Activity resides in an N‐terminal segment that is homologous to the polypeptide linker that connects the dihydrofolate synthase and dihydropteroate synthase domains in the haloarchaeal enzymes. The purified recombinant H. pylori dihydropteroate synthase was found to be a flavoprotein.