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Page 12 of 22 D’Aimmo et al. Microbiome Res Rep 2024;3:11 https://dx.doi.org/10.20517/mrr.2023.59

Figure 4. Presence of genes for the biosynthesis of chorismate, pABA, DHPPP, and THF-polyglutamate pathways and prediction of folate
synthesis from the sequenced genomes of type strains of bifidobacterial species so far described. Chorismate pathway comprises aroG
b
2.5.1.54, aroBK 4.2.3.4, aroQ 4.2.1.10, aroE 1.1.1.25, aroBK 2.7.1.71, aroA 2.5.1.19 and aroC 4.2.3.5; pABA pathway comprise pabA 2.6.1.85
c
d
and pabC 4.1.3.38; DHPP pathway comprises folE 3.5.4.16, 3.1.3.1, 3.6.1.-, folBK 4.1.2.25, folBK 2.7.63; THF-polyglud pathway comprises
folP 2.5.1.15, folC 6.3.2.12/17, dfrA 1.5.1.3. Rectangels in green: all genes of the pathway are present; rectangels in red: at least one gene of
the pathway is absent. In the right you will find the folate production prediction based on th epresence of pathwas genes: in blue:
e
predicted folate production; in yellow: pABA needed for predicted folate production; in brown, no predicted folate production; all the
genes for the biosynthesis of DHPPP are present, with the exception of alkaline phosphatase (EC 3.1.3.1). The dephosphorylation of
dihydroneopterin triphosphate into the monophosphate can occur through an alternative route using pyrophosphohydrolase number EC
3.6.1.-. which is present (Rossi 2011).
enzyme 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) responsible for DHPPP
biosynthesis, as well as the folP gene encoding dihydropteroate synthase, an enzyme involved in the
condensation of DHPPP and pABA [5,88] [Figure 2]. Therefore, it was concluded that animal species, with few
exceptions, are auxotrophic for folate, even with the presence of pABA [Figure 4]. On the other hand, most
of the bifidobacterial species from human and non-human primates have the set of fol genes but require the
supplementation of pABA .
[65]

In vitro studies for folate production
In vitro studies tested 76 strains belonging to different species of the genus Bifidobacterium, isolated from
both humans and animals, and found 17 strains to be folate-producing [62,63] . All these strains were of human
origin, thus suggesting a higher incidence of folate-producing bifidobacteria in humans as compared to
other animals, a finding confirmed by D’Aimmo et al. . These studies also confirmed folate production
[74]
variation between strains within, as well as between species.