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66c7d41500002088 ergosterol biosynthetic process

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GO-CAM Review: Ergosterol Biosynthetic Process Model (gomodel:66c7d41500002088)

Summary

This GO-CAM model represents the ergosterol biosynthetic process (GO:0006696) in Schizosaccharomyces pombe (NCBITaxon:4896). The model illustrates a comprehensive pathway of ergosterol biosynthesis with multiple enzymes, their molecular functions, cellular locations, and causal relationships between activities.

Model Structure

The model includes 15 different gene products (proteins) from S. pombe, each with defined: - Molecular functions (specific enzymatic activities) - Cellular locations (primarily in the endoplasmic reticulum or ER membrane) - Participation in the ergosterol biosynthetic process - Causal connections showing the flow of the pathway

Key Components

1. Enzymes and Activities:

  • The pathway begins with squalene synthesis (Erg9)
  • Involves multiple sterol modification enzymes (Erg1, Erg7, Erg11, etc.)
  • Includes desaturases, reductases, isomerases, and transferases
  • Ends with ergosterol as the final product

2. Cellular Localization:

  • All activities occur in the endoplasmic reticulum (GO:0005783) or more specifically in the ER membrane (GO:0005789)
  • This is consistent with what we know about sterol biosynthesis

3. Evidence:

  • Most annotations are supported by sequence similarity evidence (ECO:0000250), biological aspect of ancestor evidence (ECO:0000318), or direct experimental evidence
  • References to PMID literature and orthology to known proteins in other species (especially S. cerevisiae)

Pathway Flow Analysis

The pathway is well-structured with clear "provides input for" (RO:0002413) relationships between sequential steps:

  1. Isoprenoid synthesis → Squalene synthesis (Erg9)
  2. Squalene oxidation (Erg1) → Lanosterol synthesis (Erg7)
  3. Lanosterol modification (Erg11) → Multiple sterol intermediates
  4. Sequential sterol modifications through multiple enzymes
  5. Final steps leading to ergosterol formation

Quality Control Review

Strengths:

  1. Biological completeness: The model captures the complete ergosterol biosynthesis pathway.
  2. Molecular specificity: Appropriate molecular functions assigned to each gene product.
  3. Causal relationships: Clear "provides input for" relationships between sequential activities.
  4. Cellular context: Correct subcellular localization in the ER and ER membrane.
  5. Evidence quality: Good use of multiple evidence codes and references.

Minor issues:

  1. Duplicate causal relationships: Some activities have duplicate causal associations with the same predicate and target, one with evidence and one without. For example:
  2. Between SPBC3F6.02c (Erg26) → SPBC1709.07 (Erg27)

  3. Between SPBC16E9.05 (Erg6) → SPBC20G8.07c (Erg2)

  4. Molecular inputs/outputs: While some activities have specific chemical inputs/outputs defined (e.g., lanosterol, ergosterol), not all intermediate metabolites are explicitly defined.

  5. Regulatory connections: One positive regulation relationship exists (Ccr1 directly positively regulates Erg11), but the model could potentially benefit from additional regulatory relationships if biologically relevant.

Literature Consistency

The model uses multiple literature references (PMID:18310029, PMID:23145048, PMID:23737303, PMID:16823372) that support the ergosterol biosynthetic process in S. pombe. The enzyme functions and pathway organization are consistent with established knowledge of fungal sterol biosynthesis.

Compliance with GO-CAM Best Practices

The model follows GO-CAM best practices for representing biochemical pathways: - Each activity is enabled by a specific gene product - Activities are connected with appropriate causal predicates - Cellular components are specified - The biological process context is provided - Evidence is provided for most assertions

Parsimony and Human Understanding

The model is well-organized and represents the pathway in a way that would be clear to users familiar with sterol biosynthesis. The linear flow through sterol modifications is logically presented.

Recommendations

  1. Remove duplicate causal relationships: The duplicate causal associations without evidence should be removed.
  2. Add metabolite details: Consider adding all intermediate metabolites as inputs/outputs for a more complete representation.
  3. Verify consistency of enzyme order: Confirm that the sequence of enzyme activities matches the accepted ergosterol biosynthetic pathway in fungi.

Conclusion

This GO-CAM model (gomodel:66c7d41500002088) provides a comprehensive and scientifically accurate representation of the ergosterol biosynthetic process in S. pombe. With minor improvements to remove duplicate relationships and possibly add more metabolite details, it would be an excellent reference model for fungal sterol biosynthesis. The model is biologically sound, supported by appropriate evidence, and follows GO-CAM best practices.