Modular design

Complement (music)

Tree (set theory)

Phenotype

Enzyme

Mathematics

Bioinformatics

Metabolic engineering

Biology

Reinforcement learning

Chemical space

Gene

Image (mathematics)

Similarity (geometry)

Statistics

Machine learning

Mathematical analysis

Structural similarity

Artificial intelligence

Set (abstract data type)

Chemistry

Complementation

Synthetic biology

Monte Carlo method

Programming language

Chemical similarity

Computer science

Monte Carlo tree search

Computational biology

Drug discovery

Process (computing)

Biochemistry

ACS Synthetic Biology

Metabolic engineering aims to produce chemicals of interest from living organisms, to advance toward greener chemistry. Despite efforts, the research and development process is still long and costly, and efficient computational design tools are required to explore the chemical biosynthetic space. Here, we propose to explore the bioretrosynthesis space using an artificial intelligence based approach relying on the Monte Carlo Tree Search reinforcement learning method, guided by chemical similarity. We implement this method in RetroPath RL, an open-source and modular command line tool. We validate it on a golden data set of 20 manually curated experimental pathways as well as on a larger data set of 152 successful metabolic engineering projects. Moreover, we provide a novel feature that suggests potential media supplements to complement the enzymatic synthesis plan.

Reinforcement Learning for Bioretrosynthesis