Obsoletion request: GO:0008153 4-aminobenzoate biosynthetic process (pathway intermediate)

[ValWood]

Please provide as much information as you can:

• GO term ID and Label

4-aminobenzoate biosynthetic process (GO:0008153)
The chemical reactions and pathways resulting in the formation of 4-aminobenzoate, an intermediate in the synthesis of folic acid, a compound which some organisms, e.g. prokaryotes, eukaryotic microbes, and plants, can synthesize de novo. Others, notably mammals, cannot. In yeast, it is present as a factor in the B complex of vitamins. [PMID:11377864, ISBN:0198506732, PMID:11960743]

• Reason for deprecation Put an x in the appropriate box:

• The reason for obsoletion is a pathway intermediate.

It is also classed as an amino acid , which it doesn't appear to be (it's and intermediate in folic acid biosynthesis)

• "Replace by" term (ID and label)
  If all annotations can safely be moved to that term

• "Consider" term(s) (ID and label)
  Suggestions for reannotation

• Are there annotations to this term?

• How many EXP:

• Are there mappings and cross references to this term? (InterPro, Keywords; check QuickGO cross-references section)

• Is this term in a subset? (check the AmiGO page for that term)

• Any other information

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Checklist for ontology editor

Check term usage and metadata in Protégé

• check term usage in the ontology
• check internal mappings: RHEA, EC, MetaCyc
• check subset usage
• check taxon constraints

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Notification

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• paste the text in the ontology ticket

[pgaudet]

According to https://www.yeastgenome.org/locus/S000005316
this is a branch point?

para-aminobenzoic acid, an important intermediate for folate and ubiquinone Q biosynthesis;

We'd need to look at the folate and ubiquinone Q biosynthesis pathways to check that the starts and ends include para-aminobenzoic acid.

[ValWood]

GO:0008153 4-aminobenzoate biosynthetic process

isn't in the ubiquinone biosynthesis pathways for pombe, human or fly.

These are all curated in GO-CAM and aligned with each other:

pombase/mitochondrion#13

[ValWood]

It might be a source of 4-hydroxybenzoate for ubiquininone biosynthesis (i.e. upstream, it isn't completely known the source of 4-hydroxybenzoate in the first step) but I don't see why the process is required. It should be covered by "folic acid biosynthesis". I'm doing that pathway next which is how I spotted it. There are only 8 annotations, all "acts upstream of or within" except a single SGD annotation to ABZ1 (which is folic acid biosynthesis). It is co-annotated with folic/tetrahydrofolate biosynthesis pathway (which is correct and seems to be enough).

[ValWood]

I'll confirm this when I finish the folic acid biosynthsis pathway to be sure

[deustp01]

We'd need to look at the folate and ubiquinone Q biosynthesis pathways to check that the starts and ends include para-aminobenzoic acid.

And also taxon constraints. Mammalian ubiquinone and folate syntheses do not involve p-aminobenzoate. (Indeed, that difference is what makes sulfonamide antibiotics effective against bacteria and not lethal to humans.)

[ValWood]

Folic acid biosynthesis

https://www.pombase.org/gocam/gene/66a3e0bb00002988/SPBP8B7.29/abz1

GO:0008153 4-aminobenzoate biosynthetic process
is the first step (abz1) in the linear pathway to tetrahydrofolate
It is a precursor for folate biosynthesis.
I can't find any evidence that is it used directly in other pathways, it isn't part of
ubiquinone biosynthesis (even if the pathways of folic acid and ubiquinone are connected in some species)

P-Aminobenzoic acid (PABA) serves as an intermediate in the biosynthesis of folate in bacteria, plants, and some fungi. PMID: 1637823

Some bacteria and fungi use PABA as a precursor for secondary metabolites, including antibiotics and pigments.
Example: Certain Streptomyces species modify PABA derivatives into bioactive compounds.
It isn't a major branch point, though it seems these pathways would be modelled as beginning with PABA.

It does not appear to be directly connected to ubiqunine biosynthesis and was not used in any of the models.
It seems Chorismate is a branch point metabolite in the shikimate pathway.
It serves as a precursor for PABA (via aminodeoxychorismate synthase) and 4-hydroxybenzoate (4-HB), which is a key intermediate in ubiquinone biosynthesis.

I still think we don't need a process for PABA synthesis.

[ValWood]

OK, there is a paper that says
Marbois B, et al. (2010) para-Aminobenzoic acid is a precursor in coenzyme Q6 biosynthesis in Saccharomyces cerevisiae. J Biol Chem 285(36):27827-38
https://www.yeastgenome.org/reference/S000134552

but it isn't annotated to "ubiquinone biosynthetic process"
and "ubiquinone biosynthesis" isn't included in the models or pathways:

[ValWood]

Feature	PABA (p-Aminobenzoic Acid)	p-HBA (p-Hydroxybenzoic Acid)
Functional Group	-NH₂ (Amino)	-OH (Hydroxyl)
Role in Metabolism	Folate (Vitamin B9) biosynthesis	Ubiquinone (CoQ) biosynthesis
Source	Shikimate pathway	Shikimate or tyrosine metabolism
Occurrence	Bacteria, plants, fungi	Bacteria, plants, mammals

Chat_GPT
In the yeast Saccharomyces cerevisiae, p-aminobenzoic acid (PABA) can be utilized as a precursor for coenzyme Q (ubiquinone) biosynthesis. This process involves the deamination of PABA, where the amino group is replaced by a hydroxyl group, converting it into 4-hydroxybenzoic acid (p-HBA).
Providing as a reference
https://pmc.ncbi.nlm.nih.gov/articles/PMC4591803/

https://pubmed.ncbi.nlm.nih.gov/26260787/
The yeast Saccharomyces cerevisiae is able to use para-aminobenzoic acid (pABA) in addition to 4-hydroxybenzoic acid as a precursor of coenzyme Q, a redox lipid essential to the function of the mitochondrial respiratory chain. The biosynthesis of coenzyme Q from pABA requires a deamination reaction at position C4 of the benzene ring to substitute the amino group with an hydroxyl group. We show here that the FAD-dependent monooxygenase Coq6, which is known to hydroxylate position C5, also deaminates position C4 in a reaction implicating molecular oxygen, as demonstrated with labeling experiments. We identify mutations in Coq6 that abrogate the C4-deamination activity, whereas preserving the C5-hydroxylation activity. Several results support that the deletion of Coq9 impacts Coq6, thus explaining the C4-deamination defect observed in Δcoq9 cells. The vast majority of flavin monooxygenases catalyze hydroxylation reactions on a single position of their substrate. Coq6 is thus a rare example of a flavin monooxygenase that is able to act on two different carbon atoms of its C4-aminated substrate, allowing its deamination and ultimately its conversion into coenzyme Q by the other proteins constituting the coenzyme Q biosynthetic pathway.

I need to check which activities these are and link to ubiquinone pathway