NTR: ubiquinone biosynthetic process (New MF terms)

[sylvainpoux]

Hi GO,

while updating the ubiquinone biosynthesis pathway in human based on PMID:38425362, I realized that some terms are missing and that another term would need some update.

PMID:38425362 provides good evidence for missing steps in the pathway.

Thanks

Sylvain

First, I would like to update the name and definition of GO:0106364. Ubiquinone can have different chain length, and this term is specific for n=6, the S.cerevisiae ubiquinone. I would propose to make a generic reaction for polyprenyl, which is not species specific
FROM:
GO:0106364; F:4-hydroxy-3-all-trans-hexaprenylbenzoate oxygenase activity
4-hydroxy-3-all-trans-hexaprenylbenzoate + 2 H+ + O2 + 2 reduced [2Fe-2S]-[ferredoxin] = 3,4-dihydroxy-5-all-trans-hexaprenylbenzoate + H2O + 2 oxidized [2Fe-2S]-[ferredoxin]
TO:
GO:0106364; F:4-hydroxy-3-all-trans-polyprenylbenzoate oxygenase activity
4-hydroxy-3-all-trans-polyprenylbenzoate + 2 H+ + O2 + 2 reduced [2Fe-2S]-[ferredoxin] = 3,4-dihydroxy-5-all-trans-polyprenylbenzoate + H2O + 2 oxidized [2Fe-2S]-[ferredoxin]
Xref:
Rhea:81195
PMID:38425362

2. 2 papers show the activity of COQ4 and I would need a new GO term

Name: 4-hydroxy-3-methoxy-5-polyprenylbenzoate decarboxylase
Definition: Catalysis of the reaction: a 4-hydroxy-3-methoxy-5-(all-trans-polyprenyl)benzoate + H(+) = a 2-methoxy-6-(all-trans-polyprenyl)phenol + CO2
Child of GO:0016831 carboxy-lyase activity
Child of GO:0006744; P:ubiquinone biosynthetic process
Xref
PMID:38295803
PMID:38425362
EC 4.1.1.130
Rhea:81179

3. PMID:38425362 shows a second activity for COQ6 and I would need a new GO term
   Name: 2-methoxy-6-polyprenolphenol 4-hydroxylase
   Definition: Catalysis of the reaction: 2-methoxy-6-(all-trans-polyprenyl)phenol + 2 reduced [2Fe-2S]-[ferredoxin] + O2 + 2 H(+) = 2-methoxy-6-(all-trans-polyprenyl)benzene-1,4-diol + 2 oxidized [2Fe-2S]-[ferredoxin] + H2O

Child of GO:0016713 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced iron-sulfur protein as one donor, and incorporation of one atom of oxygen
Child of GO:0006744; P:ubiquinone biosynthetic process
Xref
EC=1.14.15.46
Rhea:81183
PMID:38425362

4. PMID:38425362 shows a new activity for COQ3 and I would need a new GO term

Name: 3-demethylubiquinone 3-O-methyltransferase
Definition: Catalysis of the reaction: a 3-demethylubiquinone + S-adenosyl-L-methionine = a ubiquinone + S-adenosyl-L-homocysteine
Child of GO:0006744; P:ubiquinone biosynthetic process
Child of GO:0008171 O-methyltransferase activity
Child of GO:0008757 S-adenosylmethionine-dependent methyltransferase activity
Xref
Rhea:81215
PMID:38425362

[sjm41]

Thanks @sylvainpoux I've recently updated other terms in this pathway, so I'll deal with this ticket too.

[sjm41]

Note: EC:4.1.1.130 and EC:1.14.15.46 are not yet available on https://enzyme.expasy.org, so these will have to be added as xrefs later.

[sjm41]

+[Term]
+id: GO:0120537
+name: 3-demethylubiquinone 3-O-methyltransferase activity
+namespace: molecular_function
+def: "Catalysis of the reaction: a 3-demethylubiquinone + S-adenosyl-L-methionine = a ubiquinone + S-adenosyl-L-homocysteine." [PMID:38425362, RHEA:81215]
+xref: RHEA:81215 {source="skos:exactMatch"}
+is_a: GO:0008171 ! O-methyltransferase activity
+is_a: GO:0008757 ! S-adenosylmethionine-dependent methyltransferase activity
+relationship: part_of GO:0006744 ! ubiquinone biosynthetic process
+property_value: term_tracker_item "#29459" xsd:anyURI
+created_by: sjm
+creation_date: 2024-12-18T09:25:15Z
+
+[Term]
+id: GO:0120538
+name: 2-methoxy-6-polyprenolphenol 4-hydroxylase activity
+namespace: molecular_function
+def: "Catalysis of the reaction: 2-methoxy-6-(all-trans-polyprenyl)phenol + 2 reduced [2Fe-2S]-[ferredoxin] + O2 + 2 H+ = 2-methoxy-6-(all-trans-polyprenyl)benzene-1,4-diol + 2 oxidized [2Fe-2S]-[ferredoxin] + H2O." [PMID:38425362, RHEA:81183]
+xref: RHEA:81183 {source="skos:exactMatch"}
+is_a: GO:0016713 ! oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced iron-sulfur protein as one donor, and incorporation of one atom of oxygen
+relationship: part_of GO:0006744 ! ubiquinone biosynthetic process
+property_value: term_tracker_item "#29459" xsd:anyURI
+created_by: sjm
+creation_date: 2024-12-18T09:30:52Z
+
+[Term]
+id: GO:0120539
+name: 4-hydroxy-3-methoxy-5-polyprenylbenzoate decarboxylase activity
+namespace: molecular_function
+def: "Catalysis of the reaction: a 4-hydroxy-3-methoxy-5-(all-trans-polyprenyl)benzoate + H+ = a 2-methoxy-6-(all-trans-polyprenyl)phenol + CO2." [PMID:38295803, PMID:38425362, RHEA:81179]
+xref: RHEA:81179 {source="skos:exactMatch"}
+is_a: GO:0016831 ! carboxy-lyase activity
+relationship: part_of GO:0006744 ! ubiquinone biosynthetic process
+property_value: term_tracker_item "#29459" xsd:anyURI
+created_by: sjm
+creation_date: 2024-12-18T09:36:09Z
+

[sjm41]

Updated term:

id: GO:0106364
name: 4-hydroxy-3-all-trans-polyprenylbenzoate oxygenase activity
namespace: molecular_function
def: "Catalysis of the reaction: 4-hydroxy-3-all-trans-polyprenylbenzoate + 2 H+ + O2 + 2 reduced [2Fe-2S]-[ferredoxin] = 3,4-dihydroxy-5-all-trans-polyprenylbenzoate + H2O + 2 oxidized [2Fe-2S]-[ferredoxin]." [PMID:38425362, RHEA:81195]
synonym: "4-hydroxy-3-all-trans-hexaprenylbenzoate oxygenase activity" NARROW []
xref: MetaCyc:RXN3O-58 {source="skos:narrowMatch"}
xref: RHEA:81195 {source="skos:exactMatch"}
is_a: GO:0016713 ! oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced iron-sulfur protein as one donor, and incorporation of one atom of oxygen
property_value: term_tracker_item "#27952" xsd:anyURI
property_value: term_tracker_item "#29459" xsd:anyURI
created_by: hjd
creation_date: 2021-02-09T15:52:26Z

[ValWood]

pinging myself @ValWood for after the hols!

[sjm41]

I just noticed that the new term we made for COQ4:

+[Term]
+id: GO:0120539
+name: 4-hydroxy-3-methoxy-5-polyprenylbenzoate decarboxylase activity
+namespace: molecular_function
+def: "Catalysis of the reaction: a 4-hydroxy-3-methoxy-5-(all-trans-polyprenyl)benzoate + H+ = a 2-methoxy-6-(all-trans-polyprenyl)phenol + CO2." [PMID:38295803, PMID:38425362, RHEA:81179]
+xref: RHEA:81179 {source="skos:exactMatch"}
+is_a: GO:0016831 ! carboxy-lyase activity
+relationship: part_of GO:0006744 ! ubiquinone biosynthetic process
+property_value: term_tracker_item "#29459" xsd:anyURI
+created_by: sjm
+creation_date: 2024-12-18T09:36:09Z

is the general instance of this existing, more specific term (that lacked any EC/RHEA xref:

id: GO:0036169
name: 3-methoxy-4-hydroxy-5-decaprenylbenzoic acid decarboxylase activity
namespace: molecular_function
def: "Catalysis of the reaction: 3-methoxy-4-hydroxy-5-decaprenylbenzoic acid -> 2-methoxy-6-decaprenylphenol + CO2." [GOC:mw, PMID:620805, PMID:7028108]
is_a: GO:0016831 ! carboxy-lyase activity
created_by: bf
creation_date: 2012-03-27T04:47:47Z
(used in a single annotation to human COQ4 by Reactome)

@pgaudet Could you merge GO:0036169 with GO:0120539 please?

[raymond91125]

GO:0036169 3-methoxy-4-hydroxy-5-decaprenylbenzoic acid decarboxylase activity has a solo Reactome TAS annotation. @deustp01 Could it be move to GO:0120539 4-hydroxy-3-methoxy-5-polyprenylbenzoate decarboxylase activity?

[sylvainpoux]

@raymond91125 @sjm41 @deustp01
I think it makes senses to only create generic reaction for polyprenyl, then we can specifiy the precise substrate using ChEBI in annotation extensions or GO-CAM models.
Thanks
Sylvain

[sjm41]

@sylvainpoux yes, fully agree we should only have the polyprenyl term here. The GO:0036169 deca term already exists, so needs to be merged into the new poly term we created.

[sjm41]

GO:0036169 3-methoxy-4-hydroxy-5-decaprenylbenzoic acid decarboxylase activity has a solo Reactome TAS annotation. @deustp01 Could it be move to GO:0120539 4-hydroxy-3-methoxy-5-polyprenylbenzoate decarboxylase activity?

@raymond91125 I believe Peter is now on vacation, but (automatically?) having this TAS annotation moved to the new GO:0120539 term should be fine.

[raymond91125]

That's good. I will merge the terms in the morning (Pacific time). Thanks.

[raymond91125]

Please let me know if there is more to be done or this is ready to be closed. Thanks.

[sjm41]

Thanks @raymond91125! We need to leave this ticket open as it's tagged as 'EC pending' (ie. waiting for new EC entries to appear in ENZYME before we can add them to some of the GO terms above)