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Pathway · 9 proteins

Folate biosynthesis

Proteins of this group that KEGG places on its “Folate biosynthesis” map for Aquifex aeolicus.

How it works

This map shows how folate, the carrier of single carbon atoms, is made from GTP, para-aminobenzoic acid and glutamate. The proteins here open the GTP ring, build the pterin and join it to para-aminobenzoate. The same starting reaction also feeds queuosine, a modified base in transfer RNA, and some proteins on this page make it.

Grouped by KEGG pathway map. The explanation above is the atlas’s own; the map itself covers more organisms than Aquifex.

Its proteins

ProteinECReaction (UniProt)Metal or clusterAmino acidsCertainty
Putative pterin-4-alpha-carbinolamine dehydratase4.2.1.96(4aS,6R)-4a-hydroxy-L-erythro-5,6,7,8-tetrahydrobiopterin = (6R)-L-erythro-6,7-dihydrobiopterin + H2O—99Step named
Dihydropteroate synthase2.5.1.15(7,8-dihydropterin-6-yl)methyl diphosphate + 4-aminobenzoate = 7,8-dihydropteroate + diphosphateMg(2+)399Step named
Aminodeoxychorismate lyase———245Step named
2-amino-4-hydroxy-6-hydroxymethyldihydropteridine pyrophosphokinase2.7.6.36-hydroxymethyl-7,8-dihydropterin + ATP = (7,8-dihydropterin-6-yl)methyl diphosphate + AMP + H(+)—160Step named
7-carboxy-7-deazaguanine synthase4.3.99.36-carboxy-5,6,7,8-tetrahydropterin + H(+) = 7-carboxy-7-carbaguanine + NH4(+)[4Fe-4S] cluster, Mg(2+)219Step named
GTP cyclohydrolase 13.5.4.16GTP + H2O = 7,8-dihydroneopterin 3'-triphosphate + formate + H(+)Zn(2+)184Step named
Riboflavin biosynthesis protein RibBA3.5.4.25; 4.1.99.12D-ribulose 5-phosphate = (2S)-2-hydroxy-3-oxobutyl phosphate + formate + H(+)D-ribulose 5-phosphate, Mg(2+), Zn(2+)406Step named
7-cyano-7-deazaguanine synthase6.3.4.207-carboxy-7-carbaguanine + NH4(+) + 2 ATP = 7-cyano-7-carbaguanine + 2 AMP + 2 diphosphate + 2 H(+)Zn(2+)218Step named
NADPH-dependent 7-cyano-7-deazaguanine reductase1.7.1.137-aminomethyl-7-carbaguanine + 2 NADP(+) = 7-cyano-7-carbaguanine + 2 NADPH + 3 H(+)—129Step named

Also part of this pathway

These proteins are described under another pathway, but also take part here.

ProteinECReaction (UniProt)Metal or clusterAmino acidsCertainty
p-aminobenzoate synthetaseHome: Aromatic amino acids———348Step named
tetrahydrofolate synthaseHome: Folate and pterin chemistry6.3.2.17(6S)-5,6,7,8-tetrahydrofolyl-(gamma-L-Glu)(n) + L-glutamate + ATP = (6S)-5,6,7,8-tetrahydrofolyl-(gamma-L-Glu)(n+1) + ADP + phosphate + H(+)Mg(2+)410Step named
6-carboxy-5,6,7,8-tetrahydropterin synthaseHome: Folate and pterin chemistry4.1.2.507,8-dihydroneopterin 3'-triphosphate + H2O = 6-carboxy-5,6,7,8-tetrahydropterin + triphosphate + acetaldehyde + 2 H(+)Zn(2+)162Step named

Origins

Could folate have been supplied before this nine-protein pathway existed?

Naturalistic proposal

None of the books searched describes a prebiotic route to folate.

Design analysis

Bacteria make folate from a pterin, para-aminobenzoic acid and glutamate; mammals cannot make it at all. Sulfa drugs, first found by Gerhard Domagk, block this pathway, and without folate a cell cannot make the precursors of DNA and RNA.

Nine proteins of the minimal set serve this pathway.

From the books: Slonczewski & Foster, Microbiology, p. 1105.

The wider question for this part of the cell: origins for manufacturing cofactors and vitamins.

Sources

Other pathways in this group: Heme and quinones · Biotin and lipoate · NAD and flavins · Thiamine and pyridoxal · Folate and pterin chemistry · Lipid and cofactor connections · Coenzyme A · Aspartate-family branches · Amino-acid connections · Folate-linked carbon transfer · Serine, glycine and sulfur · Oxidative phosphorylation · Thiamine metabolism · Pantothenate and CoA biosynthesis · Glycine, serine and threonine metabolism · Riboflavin metabolism · Nicotinate and nicotinamide metabolism · Biotin metabolism · Cysteine and methionine metabolism · Porphyrin metabolism · Pyruvate metabolism · Not yet placed in a pathway