PhyloNaP - Phylogeny for Natural Product-producing enzymes

Overview

PhyloNaP is the first large-scale resource dedicated to phylogenies of biosynthetic enzymes. The platform provides ~18,500 annotated and interactive phylogenetic trees enriched with chemical, functional, and taxonomic information. Users can classify their own sequences via phylogenetic placement, enabling functional inference in an evolutionary context.

Website: https://phylonap.cs.uni-tuebingen.de

Abstract

Phylogenetic analysis is widely used to predict enzyme function, yet building annotated and reusable trees is labor-intensive. Existing resources rarely cover secondary metabolites' synthesising enzymes and lack the biosynthetic context needed for meaningful analysis.

We present PhyloNaP, the first large-scale resource dedicated to phylogenies of biosynthetic enzymes. PhyloNaP provides ~18,500 annotated and interactive trees enriched with chemical, functional, and taxonomic information. Users can classify their own sequences via phylogenetic placement, enabling functional inference in an evolutionary context. A contribution portal allows the community to submit curated trees. By combining scale, breadth of annotation, and interactive functionality, PhyloNaP fills a major gap in bioinformatics resources for enzyme discovery and annotation, with immediate applications to secondary metabolism and beyond.

Key Features

🧬 Comprehensive Database

• ~18,500 phylogenetic trees covering bacterial biosynthetic enzymes
• Focus on tailoring enzymes from bacterial biosynthetic gene clusters (BGCs)
• Integration with MiBiG, MITE, UniProt, and antiSMASH-DB
• Both curated expert datasets and automated pipeline-generated trees

🌳 Interactive Tree Viewer

• Dynamic phylogenetic tree visualization
• Rerooting, zooming, and branch spacing adjustment
• Toggleable annotations: functional, taxonomic, BGC classifications
• Chemical structure visualization directly on trees
• Hyperlinks to reference databases (MiBiG, SwissProt, MITE, PanBGC)
• Highlighting proteins sourcing from the same BGC or Biosynthetic Gene Cluster Family (GCF) with color coding

🔍 Sequence Classification

• Phylogenetic placement of user-submitted sequences
• Visual placement results with confidence metrics

🤝 Community Contributions

• Submission portal for manually annotated trees
• Expert review process for quality assurance

Data Sources

• MiBiG: Minimum Information about a Biosynthetic Gene cluster
• MITE: Minimum Information about a Tailoring Enzyme
• UniProt: Universal Protein Resource
• antiSMASH-DB: Database of secondary metabolite biosynthetic gene clusters
• PanBGC: a user-friendly web tool to explore biosynthetic gene clusters (BGCs) diversity within Gene Cluster Families (GCFs)

Setup the Web App locally

# Clone repository
git clone https://github.com/SashaKorenskaia/PhyloNaP_WebApp.git

# create folders nesessary for database to run
mkdir PhyloNaP_data
mkdir PhyloNaP_data/tmp
mkdir PhyloNaP_data/PhyloNaP_uploads

cd PhyloNaP_data
#download and unzip the PhyloNaP database
wget https://phylonap.cs.uni-tuebingen.de/download_file

# to be able to classify query sequence, insltall docker image (make sure that the docker installed and ruuning)
docker pull sashakorenskaia/phylonap-backend



# Install Python dependencies
cd ../PhyloNaP_WebApp
conda env create -f phylonap_test.yml
conda activate phylonap_test

create a config file config_update.py inside the PhyloNaP_WebApp directory:

import os
from pathlib import Path

# Base directory setup
BASE_DIR = Path(__file__).resolve().parent.parent
DATA_DIR = os.path.join(BASE_DIR, "Phylonap_storage_local")

# Essential app configuration
PORT = int(os.environ.get("PORT", 8000))  # Using 8000 for local development
HOST = "127.0.0.1"  # localhost for local development
FLASK_DEBUG = True  # Enable debug mode for local development

# Required directory paths
TMP_DIRECTORY = os.path.join(DATA_DIR, "tmp")
DB_DIR = os.path.join(DATA_DIR, "PhyloNaP_database") #check that it matches with the directory name that you downloaded!
SQLITE_DB = os.path.join(DB_DIR, "phylonap.db")
UPLOAD_FOLDER = os.path.join(DATA_DIR, "PhyloNaP_uploads")

# SSL configuration (disabled for local development)
SSL_ENABLED = False

cd ..
python -m PhyloNaP_WebApp.app
cd PhyloNaP_WebApp

# Run application locally
flask run --host=127.0.0.1 --port=8000

Note: install the placement pipeline and the database separately — installation instructions coming soon.

The code for the protein classification pipeline available here: https://github.com/SashaKorenskaia/PhyloNaP_placement_clean

Third-Party Licenses

This product includes color specifications and designs developed by Cynthia Brewer (http://colorbrewer.org/).

This project includes third-party JavaScript libraries:

• phylotree.js by Stephen Shank and Sergei Pond (MIT License, https://github.com/veg/phylotree.js)
• Colour Palette Generator by Google (Apache License 2.0)
• ColorBrewer by Cynthia Brewer and others (Apache License 2.0)
• Solarized by Ethan Schoonover (MIT License)

License files are available in the licenses/ directory.

Citation

If you use PhyloNaP in your research, please cite:

PhyloNaP: a user-friendly database of Phylogeny for Natural Product-producing enzymes Aleksandra Korenskaia, Judit Szenei, Lisa Vader, Kai Blin, Tilmann Weber, Nadine Ziemert bioRxiv 2025.09.23.677986; doi: https://doi.org/10.1101/2025.09.23.677986

Contact

Mail: For questions or feedback, please contact us at [email protected]

Ziemert Lab, University of Tübingen, Germany

License

PhyloNaP is released under the MIT License. The software is free to use for academic and commercial purposes.

Contributing

We welcome community contributions! Please see our contribution guidelines and use the submission portal on the website to add your curated phylogenetic trees.