Prediction and Design of Novel Metabolic Pathways for the Production of Desired Chemicals

Many systematic platforms have been developed in the past decades to predict the metabolic pathways for efficient production of desired chemicals. Here, we developed the framework to generate pathways and suggests enzyme candidates through prioritization process to evaluate feasibility of novel pathways. The systematic framework consists of two parts, route generation and prioritization process. Route generation process generates pathways based on the reaction rule sets which were constructed based on the logics acquired from analysis of reaction mechanism of existing biochemical reactions. After route generation, five prioritization factors, binding site covalence, chemical similarity, thermodynamic favorability, pathway distance and organism specificity are evaluated to estimate the feasibility of generated reaction pathways. As a validation, novel synthetic pathways for the three chemicals, isobutanol, 3-hydroxypropionate (3HP) and butyryl-CoA, were predicted using our system to evaluate the capacity and reliability of the framework. This systematic framework should be an additional resource useful for the practice of synthetic biology and metabolic engineering.[This work was supported by the Technology Development Program to Solve Climate Changes on Systems Metabolic Engineering for Biorefineries from the Ministry of Science, ICT and Future Planning (MSIP) through the National Research Foundation (NRF) of Korea (NRF-2012-C1AAA001-2012M1A2A2026556).]