An alternative pathway for reduced folate biosynthesis in bacteria and halophilic archaea.
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.
Levin
Itay
I
Department of Molecular Microbiology and Biotechnology, Tel Aviv University, Tel Aviv, 69978, Israel.
Giladi
Moshe
M
Altman-Price
Neta
N
Ortenberg
Ron
R
Mevarech
Moshe
M
D000595:Amino Acid Sequence; D001105:Archaea / Q000235:genetics* / Q000378:metabolism; D019843:Archaeal Proteins / Q000235:genetics / Q000502:physiology; D001419:Bacteria / Q000235:genetics* / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology; D017124:Conserved Sequence; D004094:Dihydropteroate Synthase / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics / Q000502:physiology; D005420:Flavoproteins / Q000737:chemistry / Q000302:isolation & purification; D005492:Folic Acid / Q000096:biosynthesis*; D017353:Gene Deletion; D005816:Genetic Complementation Test; D019614:Haloarcula marismortui / Q000235:genetics / Q000378:metabolism; D019617:Halobacterium salinarum / Q000235:genetics / Q000378:metabolism; D019622:Haloferax volcanii / Q000235:genetics / Q000502:physiology; D016480:Helicobacter pylori / Q000235:genetics / Q000502:physiology; D008969:Molecular Sequence Data; D010453:Peptide Synthases / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000235:genetics / Q000502:physiology; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics / Q000378:metabolism
D019843:Archaeal Proteins; D001426:Bacterial Proteins; D005420:Flavoproteins; D011994:Recombinant Proteins; D005492:Folic Acid; D013762:Tetrahydrofolate Dehydrogenase; D004094:Dihydropteroate Synthase; D010453:Peptide Synthases; C020041:dihydrofolate synthetase