Check out our latest paper Chemoenzymatic Multistep Retrosynthesis with Transformer Loops in RSC Chemical Science!

In this study, we developed the triple-transformer loop algorithm with biocatalysis (TTLAB) as a new tool for computer-aided synthesis planning (CASP). TTLAB integrates chemical reactions and biocatalysis to perform single-step retrosynthesis and propose efficient multistep chemoenzymatic routes. This approach enables the design of greener, more selective synthetic pathways, including enantioselective biocatalytic steps.

Abstract

Integrating enzymatic reactions into computer-aided synthesis planning (CASP) should help devise more selective, economical, and greener synthetic routes. Herein we report the tripletransformer loop algorithm with biocatalysis (TTLAB) as a new CASP tool for chemoenzymatic multistep retrosynthesis. Single-step retrosyntheses are performed using two triple transformer loops (TTL), one trained with chemical reactions from the US Patent Office (USPTO-TTL), the second one obtained by multitask transfer learning combining the USPTO dataset with preparative biotransformations from the literature (ENZR-TTL). Each TTL performs single-step retrosynthesis independently by tagging potential reactive sites in the product, predicting for each site possible starting materials (T1) and reagents or enzymes (T2), and validating the predictions via a forward transformer (T3). TTLAB combines predictions from both TTLs to explore multistep sequences using a heuristic best-first tree search and propose short routes from commercial building blocks including enantioselective biocatalytic steps. TTLAB can be used to assist chemoenzymatic route design.

Author(s) David Kreutter and Jean-Louis Reymond