Machine learning-enabled retrobiosynthesis of molecules

Retrobiosynthesis provides an effective and sustainable approach to producing functional molecules. The past few decades have witnessed a rapid expansion of biosynthetic approaches. With the recent advances in data-driven sciences, machine learning (ML) is enriching the retrobiosynthesis design toolbox and being applied to each step of the synthesis design workflow, including retrosynthesis planning, enzyme identification and engineering, and pathway optimization. The ability to learn from existing knowledge, recognize complex patterns and generalize to the unknown has made ML a promising solution to biological problems. In this Review, we summarize the recent progress in the development of ML models for assisting with molecular synthesis. We highlight the key advantages of ML-based biosynthesis design methods and discuss the challenges and outlook for the further development of ML-based approaches.