Metabolic Engineering of Escherichia coli for the Production of 2-Hydroxyacids Containing Polyhydroxyalkanoates

Polyhydroxyalkanoates (PHAs) are bacterial polyesters having biodegradability, biocompatibility and general mechanical properties of plastics. In PHAs biosynthesis, the key enzyme is PHA synthase that polymerizes hydroxyacyl-CoAs into PHAs. PHA synthases show activity for broad range of substrates which are more than 150 kinds of 3-, 4-, 5- and 6-hydroxyacyl-CoAs. However, there is no report about PHAs containing 2-hydroxyacids in nature and PHA synthase showed negligible activity for lactate (2-hydroxypropionate). Here, we produced non-natural substrate, 2-hydroxyacids such as lactate, 2-hydroxybutyrate containing PHAs with engineered PHA synthase from Pseudomonas sp. MBEL 6-19 and engineered propionyl-CoA transferase from Clostridium propionicum. For production from unrelated carbon sources such as glucose, systems metabolic engineering was conducted to redirect and concentrate the metabolic flux toward the 2-hydroxyacids based on the in silico simulation with heterogeneous metabolic pathways harboring propionyl-CoA transferase and evolved PHA synthase for polymerization. It suggests the sustainable plastic production process which can replace the current chemical process. [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)].