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Obsoletion request: homoserine biosynthetic process GO:0009090 #28911

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Antonialock opened this issue Sep 12, 2024 · 9 comments
Open
11 tasks

Obsoletion request: homoserine biosynthetic process GO:0009090 #28911

Antonialock opened this issue Sep 12, 2024 · 9 comments
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@Antonialock
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Antonialock commented Sep 12, 2024

Please provide as much information as you can:

  • GO term ID and Label
    homoserine biosynthetic process GO:0009090

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

  • [x ] The reason for obsoletion is that this term was an unnecessary grouping term.

The reason for obsoletion is that this represents an intermediate (branch point)

  • "Replace by" term (ID and label)

threonine biosynthesis + de novo methionine biosynthesis

  • "Consider" term(s) (ID and label)
    threonine biosynthesis + de novo methionine biosynthesis

  • Are there annotations to this term?

Homoserine is a toxic intermediate in the pathway that converts aspartate to threonine OR methionine; homoserine sits at the branch point of the pathway and can either be phosphorylated which leads it down the threonine biosynthesis route or acetylated which leads it towards methionine.

I don't think "homoserine biosynthesis" represents a GO biological programme, it's just an intermediate in the pathway. Genes that are part of this pathway should either be annotated to 1. de novo methionine biosynthesis or 2. to threonine biosynthesis, or 3. to both these terms if upstream of homoserine.

i.e. in the iagram below; keep the blue and the purple branches of the pathway, but remove the red

366876984-3c0194d9-74b8-437f-aa1f-5e9ce18f53a5

https://link.springer.com/article/10.1007/s00726-014-1873-1


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

Check annotations

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@raymond91125
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I don't think "homoserine biosynthesis" represents a GO biological programme, it's just an intermediate in the pathway. Genes that are part of this pathway should either be annotated to 1. de novo methionine biosynthesis or 2. to threonine biosynthesis, or 3. to both these terms if upstream of homoserine.

Is it desirable to always make 2 separate annotations for Hom[2/3/6]p. Following the logic, isn't it reasonable to also include isoleucine biosynthesis as the 3rd?

@ValWood
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ValWood commented Sep 13, 2024

As I build pathways I am making a list of processes that appear to be spurious.

GO:0071269 L-homocysteine biosynthetic process
GO:0009092 homoserine metabolic process

are on my list

@ValWood
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ValWood commented Sep 13, 2024

Although I am not sure how this fits with the existing discussions about representing branch points. Maybe that rule only applies to more "linear" pathways. It is interesting that me and @Antonialock came to the same conclusion. It would be useful to wait to see what @rozaru thinks about this one when she gets to it.

I don't think we would include isoleucine biosynthesis because this is clearly an end point,

@deustp01
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One approach would be to consult a comprehensive textbook of biochemistry like Devlin and use the pathway boundaries defined there to identify / individuate GO process boundaries and identify the defining inputs and outputs. This at least represents a biochemistry community consensus. To the extent that these boundaries are arbitrary, we can at least be consistently arbitrary.

@raymond91125
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I cannot find homoserine or the synthesis of threonine in "Textbook of Biochemistry with Clinical Correlation (4th ed.)". Devlin does not appear to describe essential AA synthesis. Are there some other standard textbooks where I should be looking for these defined pathways?
I'd argue against references that are not digitized, archived, and readily accessible on the internet, though.
Should we include this issue in a more general pathway start/end discussion? @pgaudet Thanks.

@Antonialock
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Antonialock commented Sep 14, 2024

Is it desirable to always make 2 separate annotations for Hom[2/3/6]p. Following the logic, isn't it reasonable to also include isoleucine biosynthesis as the 3rd?

@raymond91125 I think that would be redundant since isoleucine is made from threonine; it ”follows on” from threonine, and is not made from a separate branch in the pathway. Threonine seems important enough to be its own module (being an essential building block and all) even though it’s arbitrary for sure where things start and end.

In papers, isoleucine is “always” shown as a dashed line in the pathway; I interpret that as it being thought of as a downstream module. Similarly I wouldn’t annotate the citric acid cycle to threonine biosynthesis even though it provides the ocaloacetate to make the aspartate to make threonine.

I cannot find homoserine or the synthesis of threonine in "Textbook of Biochemistry with Clinical Correlation (4th ed.)".

I guess it is not in a clinical textbook since it is a microbe (and plant?) specific pathway
This is how Stryer represents it p.1003 in Biochemistry. Note how they use separate arrows for threonine and methionine biosynthesis even though the start of those two pathways (hom2/3/6) are the same

IMG_1633

https://biokamikazi.wordpress.com/wp-content/uploads/2013/10/biochemistry-stryer-5th-ed.pdf

(also, might be important to be aware of; lysine is made by a different pathway in fungi, it's bacteria that make it from aspartate, so there are differences between kingdoms. The specific steps in methionine biosynthesis also differ within fungi, I don't know if this is important for GO annotation)

@raymond91125
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@Antonialock Thanks for providing additional information. Personally I prefer minimizing pathways overlapping with one another. But the most important thing is to try to be consistent within GO.

@sjm41
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sjm41 commented Sep 16, 2024

Not sure this helps, but GO:0009090 is xreffed to MetaCyc:HOMOSERSYN-PWY:

Screenshot 2024-09-16 at 17 03 02

@pgaudet
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pgaudet commented Sep 16, 2024

Proposal from ontology call @raymond91125 @edwong57 @sjm41 : keep homoserine biosynthetic process because it is a branch point

See also discussion here: #22542 (comment)

We need to make a (final) decision and document it.

Actions:

  • describe starts and ends of homoserine, methionine, and threonine biosynthetic process as defined by MetaCyc
  • maybe check if annotations are consistent ?
  • add has_part 'homoserine biosynthetic process' to methionine, and threonine biosynthetic process

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