https://www.biorxiv.org/content/10.1101/2024.11.04.621673v2
BioPKS Pipeline is a combined retrobiosynthesis pipeline intended to expand the design space of feasible biosynthetic pathways between simple, inexpensively available precursors and high-value small molecules. BioPKS Pipeline has been developed by integrating two software packages: RetroTide, which specializes in modular polyketide synthase (PKS) retrobiosynthesis, and DORAnet, tailored for singular enzymatic synthesis. With BioPKS Pipeline, users will first specify the target molecule for which they wish to discover biosynthetic pathways. Subsequently, users will have the option of either performing PKS retrobiosynthesis first and then a DORAnet expansion or vice versa - though the former sequence is a more common occurrence in metabolic engineering given that there are only a couple of starter molecules that PKSs can accept (such as Malonyl-CoA).
When a target molecule cannot be reached by RetroTide, i.e. by PKSs alone, DORAnet will accept the PKS product that is closest to the downstream target as an input and perform a network expansion to reach the target. This network expansion involves recursively applying either biological or chemical reaction rules for a predetermined number of steps. If DORAnet fails to find pathways between the PKS product and the final product, users can move onto other PKS designs instead, which may generate PKS products that DORAnet can indeed transform into the final product. If the other PKS designs still fail to reach the final product, DORAnet will run a reverse expansion on the final target molecule to generate a list of upstream precursors. For each precursor in this list, Retrotide will be deployed to generate PKS designs to synthesize these precursors.
To begin using BioPKS pipeline, we have provided a couple of tutorials under notebooks/tutorials/, which may be useful to follow.
Users can install BioPKS Pipeline by first creating a Python 3.10 conda environment and then using pip to directly install the package:
conda create -n BioPKS_py310_env python=3.10
pip install -e.
We have also created a dockerfile for users to run BioPKS Pipeline within a containerized environment. To begin, run the following command in the same directory as the dockerfile:
docker build -t biopks_pipeline .
After building the docker image locally, spin up a container with an interactive bash shell:
docker run -ti biopks_pipeline /bin/bash
In this interactive bash shell, within the scripts folder, run the example script:
python run 00_run_example_pks_bio.py