RetroBioCat as a computer-aided synthesis planning tool for biocatalytic reactions and cascades

Abstract

As the enzyme toolbox for biocatalysis has expanded, so has the potential for the construction of powerful enzymatic cascades for efficient and selective synthesis of target molecules. Additionally, recent advances in computer-aided synthesis planning are revolutionizing synthesis design in both synthetic biology and organic chemistry. However, the potential for biocatalysis is not well captured by tools currently available in either field. Here we present RetroBioCat, an intuitive and accessible tool for computer-aided design of biocatalytic cascades, freely available at retrobiocat.com. Our approach uses a set of expertly encoded reaction rules encompassing the enzyme toolbox for biocatalysis, and a system for identifying literature precedent for enzymes with the correct substrate specificity where this is available. Applying these rules for automated biocatalytic retrosynthesis, we show our tool to be capable of identifying promising biocatalytic pathways to target molecules, validated using a test set of recent cascades described in the literature. Biocatalytic methods are lacking in current computer-aided synthesis planning tools. Now, RetroBioCat allows computer-aided design of biocatalytic cascades for organic synthesis and synthetic biology. The program was validated using reported cascades and is freely available at retrobiocat.com.