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Page 4 of 22 D’Aimmo et al. Microbiome Res Rep 2024;3:11 https://dx.doi.org/10.20517/mrr.2023.59

Figure 1. The chemical structure of folic acid (mono-glutamate derivate). PABA: Para-aminobenzoic acid.

Figure 2. Shikimate and folate biosynthesis pathway and relevant enzymes and genes involved. Metabolites: I: D-erythrose 4-phosphate;
II: phosphoenolpyruvate; III: 7-phosphate-2-dehydro-3-deoxy-D-arabinoheptonate; IV: 3-dehydroquinate; V: 3-dehydroshikimate; VI:
shikimate; VII: shikimate 3-phosphate; VIII: 5-O-(1-carboxyvinyl)-3-phosphoshikimate. Enzymes: EC 2.15.1.54: 3-deoxy-7-
phosphoheptulonate synthase; EC 4.2.3.4: 3-dehydroquinate synthase; EC 4.2.1.10: 3-dehydroquinate dehydratase I; EC 1.1.1.25:
shikimate dehydrogenase; EC 2.7.1.71: shikimate kinase; EC 2.5.1.19: 3-phosphoshikimate 1-carboxyvinyltransferase; EC 4.2.3.5:
chorismate synthase; EC 2.6.1.85: aminodeoxychorismate synthase; EC 4.1.3.38: aminodeoxychorismate lyase; EC 3.5.4.16: guanosine
triphosphate (GTP) cyclohydrolase; EC 3.6.1.67: dihydroneopterin triphosphate diphosphatase; EC 4.1.2.25: dihydroneopterin aldolase;
EC 2.7.6.3: 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine diphosphokinase; EC 2.5.1.15: dihydropteroate synthase; EC 6.3.2.12:
dihydrofolate synthase; EC 6.3.2.17: tetrahydrofolate synthase; EC 1.5.1.3: dihydrofolate reductase. In circles, genes are involved in folate
*
biosynthesis. Enzymes common to mammals.

[26]
enterocytes is led by a proton-coupled folate transporter responsible for the intestinal uptake of folate . In
contrast to folate from foods or gut microbiota, synthetic folic acid, once in the enterocyte cytoplasm, must