Predicting enzymatic reactions with a molecular transformer

• Published in: Chemical science (Cambridge) Vol. 12; no. 25; pp. 8648 - 8659
• Main Authors: Kreutter, David, Schwaller, Philippe, Reymond, Jean-Louis
• Format: Journal Article
• Language: English
• Published: England Royal Society of Chemistry 01-07-2021; The Royal Society of Chemistry
• Subjects: Chemistry; Enzymes; Machine learning; Mutation; Reaction products; Reagents; Route selection; Stereochemistry; Transformers
• ISSN: 2041-6520; 2041-6539
• DOI: 10.1039/d1sc02362d

The use of enzymes for organic synthesis allows for simplified, more economical and selective synthetic routes not accessible to conventional reagents. However, predicting whether a particular molecule might undergo a specific enzyme transformation is very difficult. Here we used multi-task transfer learning to train the molecular transformer, a sequence-to-sequence machine learning model, with one million reactions from the US Patent Office (USPTO) database combined with 32 181 enzymatic transformations annotated with a text description of the enzyme. The resulting enzymatic transformer model predicts the structure and stereochemistry of enzyme-catalyzed reaction products with remarkable accuracy. One of the key novelties is that we combined the reaction SMILES language of only 405 atomic tokens with thousands of human language tokens describing the enzymes, such that our enzymatic transformer not only learned to interpret SMILES, but also the natural language as used by human experts to describe enzymes and their mutations.
The enzymatic transformer was trained with a combination of patent reactions and biotransformations and predicts the structure and stereochemistry of enzyme-catalyzed reaction products with remarkable accuracy.