Reinforcement Learning for Bioretrosynthesis

ACS Synth Biol. 2020 Jan 17;9(1):157-168. doi: 10.1021/acssynbio.9b00447. Epub 2019 Dec 30.


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.

Keywords: Monte Carlo Tree Search; metabolic engineering; pathway design; reinforcement learning; retrosynthesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Artificial Intelligence*
  • Enzymes / chemistry
  • Enzymes / metabolism
  • Markov Chains
  • Metabolic Engineering / methods*
  • Metabolic Networks and Pathways*
  • Models, Biological*
  • Monte Carlo Method
  • Reinforcement, Psychology*
  • Software
  • Synthetic Biology / methods


  • Enzymes