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Based on my review of the GO-CAM model and the scientific literature, I'll now provide a comprehensive review of gomodel:62b4ffe300002470 "Ochratoxin A biosynthesis & catabolism (A. niger)".

Review of GO-CAM Model: 62b4ffe300002470

General Overview

This model depicts the ochratoxin A (OTA) biosynthesis and catabolism pathways in Aspergillus niger. The model focuses on the enzymes involved in both the production and breakdown of this important mycotoxin. Ochratoxin A is a significant food contaminant produced by various Aspergillus and Penicillium species that has nephrotoxic, immunotoxic, genotoxic, neurotoxic, and teratogenic properties.

Model Structure and Content

The model includes five molecular activities involving four proteins:

  1. A2R6H1 (OtaA) - a polyketide synthase involved in the initial steps of OTA biosynthesis
  2. A2R6H0 (OtaB) - a non-ribosomal peptide synthetase
  3. A2R6G9 (OtaC) - a cytochrome P450 oxidoreductase
  4. A2R2V4 (Am2) - a carboxypeptidase involved in OTA degradation

The biosynthesis pathway is represented as a linear chain of activities connected by "provides input for" (RO:0002413) relationships, while the catabolism pathway is represented separately.

Detailed Assessment

Strengths

  1. Pathway Completeness: The model provides a comprehensive representation of both OTA biosynthesis and catabolism, making it scientifically valuable.

  2. Molecular Functions: The molecular functions assigned to each protein are correct and supported by literature.

  3. Chemical Inputs/Outputs: The inputs and outputs for most reactions are properly specified, with appropriate ChEBI IDs.

  4. Causal Connections: The model correctly uses the "provides input for" (RO:0002413) relationship to connect activities in the biosynthetic pathway.

Areas for Improvement

  1. Missing Molecular Details: The role of A2R6G7 (OtaD) is missing from the model, though it's mentioned in the literature as the final enzyme in the pathway that chlorinates ochratoxin B to form ochratoxin A.

  2. Incomplete Input/Output Specifications:

  3. OtaC (A2R6G9) lacks a specified input and output, which should include 7-methylmellein as input and 7-carboxymellein as output.

  4. OtaB (A2R6H0) has L-phenylalanine as input but lacks a specified output (which should be ochratoxin B).

  5. Cellular Location Information: Only one activity (A2R2V4 carboxypeptidase) specifies a cellular location (extracellular region). According to literature, this is correct, but location information for the other proteins would enhance the model.

  6. Evidential Support: Most activities cite the same evidence source (PMID:27667988), which is appropriate, but for the carboxypeptidase activity, an additional reference (PMID:24947135) is used that specifically demonstrates the ochratoxinase activity of Am2.

  7. Missing Connection: There is no explicit connection between the biosynthesis and catabolism pathways in the model, which could be added to make the model more complete.

Compliance with GO-CAM Best Practices

The model generally follows GO-CAM best practices:

  1. Proper Use of Relationship Types: The causal relationships between activities use the appropriate "provides input for" (RO:0002413) predicate.

  2. Appropriate Evidence Codes: Evidence codes (ECO:0000304 for author statement and ECO:0000314 for direct assay) are used appropriately.

  3. Proper Molecular Function Assignment: The molecular functions are correctly assigned to each protein based on their characterized biochemical activities.

  4. Biological Context: Each activity is correctly placed within the appropriate biological process (either ochratoxin A biosynthetic process or ochratoxin A catabolic process).

However, based on the "How to annotate complexes in GO-CAM" document, if any of these enzymes function as part of complexes, that should be represented. The current literature doesn't indicate that these enzymes function as complexes, so the current representation is appropriate.

Recommendations for Improvement

  1. Add the missing OtaD activity: Include the role of A2R6G7 (OtaD) as the enzyme that chlorinates ochratoxin B to form ochratoxin A, connecting it after OtaB in the pathway.

  2. Complete input/output specifications: Add the missing inputs and outputs for OtaC and OtaB to make the model chemically complete.

  3. Enhance cellular location information: Add cellular location information for the biosynthetic enzymes if available in the literature.

  4. Connect biosynthesis and catabolism: Consider adding a relationship that connects the end of the biosynthesis pathway to the beginning of the catabolism pathway, to show the complete lifecycle of ochratoxin A.

  5. Expand evidential support: Consider incorporating additional references that specifically characterize each enzyme's role in the pathway.

Conclusion

The GO-CAM model 62b4ffe300002470 is a valuable representation of ochratoxin A biosynthesis and catabolism in Aspergillus niger. While it has a few areas that could be improved for completeness, it correctly represents the core pathway and follows GO-CAM best practices. With the suggested enhancements, it would provide an even more comprehensive and accurate representation of this important mycotoxin pathway.