wildkcat 0.0.3

Extract, Retrieve and Predict kcat values for a metabolic model to run enzyme constrained metabolic pipelines.

WILDkCAT

WILDkCAT is a set of scripts designed to extract, retrieve, and predict enzyme turnover numbers (kcat) for genome-scale metabolic models.

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Installation

Install WILDkCAT directly from PyPI:

pip install wildkcat

Environment Setup

Provide your BRENDA login credentials and Entrez API email adress to query the BRENDA enzyme database and NCBI database.

Create a file named .env in the root of your project with the following content:

ENTREZ_EMAIL=[e-mail]
BRENDA_EMAIL=[e-mail]
BRENDA_PASSWORD=your_password

[!IMPORTANT]

• Replace the placeholders with the credentials from the account you created on the BRENDA website.
• Ensure this file is not shared publicly (e.g., add .env to your .gitignore) since it contains sensitive information.
• The scripts will automatically read these environment variables to authenticate and retrieve kcat values.

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Usage

WILDkCAT can be used as scripts or via the CLI.

Command-Line Interface (CLI)

After installation, you can use the WILDkCAT CLI:

wildkcat --help

Example Workflow:

# Extract kcat data
wildkcat wildkcat extraction \
    path/to/my_model.json \
    path/to/kcat_data.tsv

# Retrieve kcat values from databases
wildkcat retrieval \
    path/to/kcat_data.tsv \
    path/to/kcat_retrieved.tsv \
    "Organism name" \
    20 30 \  # Temperature range
    6.5 8.5 \  # pH range

# Generate input for CataPro
wildkcat prediction-part1 kcat_data_retrieved.csv \
    prediction_input.csv \
    7  # Limit matching score 

# Integrate CataPro prediction 
wildkcat prediction-part2 kcat_retrieved.tsv 
    prediction_output.csv \
    substrate_to_smiles.tsv \
    kcat_final.tsv \
    7  # Limit matching score

# Generate summary report
wildkcat report  path/to/my_model.json
    kcat_final.tsv

[!WARNING]
Currently, the SABIO-RK database is experiencing server overload and queries can be very slow, especially for large models. In these cases, it is recommended to use only the 'brenda' database in the retrieval command.

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Programatic Access

from wildkcat import run_extraction, run_retrieval, run_prediction_part1, run_prediction_part2, generate_summary_report

Example: E. coli Core Model

A ready-to-run example is available here. It demonstrates a full extraction, retrieval, and prediction workflow on the E. coli core model.

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Key functions

extract_kcat.py

• Verifies whether the reaction EC number exists.
• Retains inputs where reaction-associated genes/enzymes are not supported by KEGG.
• Retains inputs where no enzymes are provided by the model.

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retrieve_kcat.py

• If multiple enzymes are provided, searches UniProt for catalytic activity.
• If multiple catalytic enzymes are identified, store all.
• When multiple enzymes are found, computes identity percentages relative to the identified catalytic enzyme.
• Applies Arrhenius correction to values within the appropriate pH range.
• For rows with multiple scores, selects:
  • The best score
  • The highest identity percentage
  • The lowest kcat value

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predict_kcat.py

• If multiple enzymes are provided, searches UniProt for catalytic activity.
• Skips entries missing KEGG compound IDs.

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Feedback & Improvements

Contributions, suggestions, and feedback are very welcome! If you encounter any issues, have ideas for new features, or notice room for improvement, feel free to open an issue or submit a pull request.