Skip to content

62b4ffe300002544 Ilicicolin H Neonectria sp strain DH2

Now, let me review the GO-CAM model in light of the information gathered:

GO-CAM Model Review: gomodel:62b4ffe300002544

Overview

The model titled "Ilicicolin H (Neonectria sp. strain DH2)" describes the biosynthetic pathway of ilicicolin H, a potent antifungal compound that inhibits the mitochondrial cytochrome bc1 complex. The model includes activities of four proteins (IliA, IliB, IliC, and IliD) encoded in the ilicicolin H biosynthetic gene cluster in Neonectria sp. strain DH2.

Biological Content and Literature Support

The model is well-supported by the scientific literature, particularly the paper by Lin et al. (PMID:31216742), which describes the identification and characterization of the ilicicolin H biosynthetic gene cluster. The pathway depicted in the model aligns with the mechanism proposed in this paper, where:

  1. IliA (P0DO30) functions as a hybrid PKS-NRPS synthetase
  2. IliB (P0DO31) functions as a trans-enoyl reductase
  3. IliC (P0DO32) functions as a cytochrome P450 monooxygenase
  4. IliD (P0DO33) functions as a Diels-Alderase

The model accurately represents the biosynthetic steps and chemical transformations described in the paper.

Molecular Functions and Associations

The model includes appropriate molecular functions for each protein:

  • IliA: GO:0016218 (polyketide synthase activity), GO:0016491 (oxidoreductase activity), and GO:1904091 (non-ribosomal peptide synthetase activity)
  • IliB: GO:0016631 (enoyl-[acyl-carrier-protein] reductase activity)
  • IliC: GO:0016491 (oxidoreductase activity)
  • IliD: GO:0009975 (cyclase activity)

All activities are appropriately part of GO:0140781 (ilicicolin H biosynthetic process).

Causal Associations

The model includes several causal associations using appropriate predicates: - IliB's enoyl-reductase activity positively regulates (RO:0002629) IliA's polyketide synthase activity - IliA's non-ribosomal peptide synthetase activity provides input for (RO:0002413) IliA's oxidoreductase activity - IliA's oxidoreductase activity provides input for (RO:0002413) IliC's oxidoreductase activity

These causal links correctly represent the flow of the biosynthetic pathway according to the literature.

Input-Output Relationships

The model correctly represents substrate-product relationships: - IliA works with tyrosine (CHEBI:17895) and produces an intermediate (CHEBI:155890) - IliC uses this intermediate (CHEBI:155890) as input and produces another intermediate (CHEBI:155889) - IliD uses this second intermediate (CHEBI:155889) as input and produces ilicicolin H (CHEBI:77772)

Quality Assessment

Strengths:

  1. The model accurately represents the ilicicolin H biosynthetic pathway as described in the literature
  2. All proteins have appropriate molecular functions
  3. Input and output molecules are correctly specified
  4. Causal relationships between activities are logically connected
  5. All assertions are supported by evidence from the literature (PMID:31216742)

Suggested Improvements:

  1. Missing chemical inputs: While the model shows some inputs like tyrosine, acetyl-CoA, and malonyl-CoA, it could be more specific about all the building blocks (S-adenosyl-L-methionine is mentioned in the paper as contributing methyl groups)

  2. Incomplete causal associations: The model could be improved by adding a causal association between IliC's oxidoreductase activity and IliD's cyclase activity to complete the pathway flow

  3. Molecular function clarity: For IliA, which has multiple activities, the model could be more specific about which domain is responsible for each function

Conformance to GO-CAM Best Practices

The model generally conforms to GO-CAM best practices: - All activities are enabled by specific gene products - Each activity has an appropriate GO molecular function term - Each activity is part of a relevant biological process - Evidence codes and references are provided for assertions - Input and output molecules are specified where appropriate

Conclusion

The GO-CAM model gomodel:62b4ffe300002544 is a high-quality representation of the ilicicolin H biosynthetic pathway in Neonectria sp. strain DH2. It is well-supported by the literature and follows most GO-CAM best practices. Minor improvements could be made to enhance the completeness of the causal associations and input specifications, but overall, the model provides a clear and accurate description of this biosynthetic pathway.