Identification of metabolites identical and similar to drugs as candidates for metabolic engineering

Natural compounds and derivatives play an essential role in the pharmaceutical industry, however, the difficulty in resynthesizing natural products or isolate them from the native host, often limit their availability, elevate costs and slow down the pharmaceutical manufacturing process. In this context, application of synthetic biology could enable the efficient production of large amounts of drugs or drug precursors in heterologous microorganisms aiming to accelerate the entire manufacturing process. Considering this perspective, here we developed a pipeline to automatically search for metabolites available in the metabolic space that are structurally similar to worldwide approved drugs. This pipeline involved the in silico screening of metabolites from a metabolic pathway meta-database using both Tanimoto coefficients based on Daylight like fingerprints and Maximum Common Substructure algorithm. The method was successfully applied to identify metabolites sharing essential scaffolds with one or more drugs as potential candidates for metabolic engineering. Three of these metabolites (Festuclavine, Scopolamine, and Baccatin III) were identified as similar to many drugs like Cabergoline, Oxitropium, Paclitaxel and had their metabolic pathways computationally mapped for their production in Saccharomyces cerevisiae with our proprietary pathway design software. These compounds are examples of new opportunities for the application of synthetic biology in pharmaceutical production.