Design of Novel Biosynthetic Pathways for the Production of Industrially Valuable Chemicals

There have been many efforts in developing systematic platforms to predict novel metabolic pathways for the efficient production of industrially desirable chemicals. In this need, we developed a systematic framework which generates metabolic pathways along with their candidate enzymes in order to identify feasible and most efficient biosynthetic pathways for the target chemicals. This platform largely consists of two parts, route generation and prioritization process. Route generation process generates pathways based on reaction rule sets which were constructed based on the logics acquired from the analysis of reaction mechanisms of existing biochemical reactions observed in biological systems. After route generation, two prioritization factors, including chemical similarity, thermodynamic favorability were evaluated to estimate the feasibility of each generated reaction pathway from the framework. Using this framework, several novel pathways have been designed to produce valuable chemicals. To validate this framework, novel biosynthetic pathways for 3-hydroxypropionate (3HP), acrylic acid, toluene and other several chemicals were predicted using this system. This systematic framework should be an valuable resource useful for the advance 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-2012M1A2A2026556 and NRF-2012M1A2A2026557).]