Chemical Engineering Science, Vol.103, 109-114, 2013
Redirecting carbon flux into malonyl-CoA to improve resveratrol titers: Proof of concept for genetic interventions predicted by OptForce computational framework
Malonyl-CoA is the limiting precursor for the overexpression of an array of heterologous pathways in bacteria, such as flavanones, polyketides, microdiesel and poly unsaturated omega-3 fatty acids. Previously, we have been able to develop a strain with higher carbon flux to acetyl-coA and malonyl-CoA by carrying out genetic interventions predicted by OptForce framework. Here we carried out the same interventions in a resveratrol producing strain and obtained a 60% increase in the yield giving the highest titer of 1.6 g/L obtained in lab scale fermentation without the addition of expensive fatty acid pathway inhibitors such as cerulenin. The positive genetic alterations involved overexpression of pyruvate dehydrogenase multi enzyme complex (PDH), phosphoglycerate kinase (PGR), glyceraldehyde-3-phosphate dehydrogenase (GapA) and deletion of fumarase (FumC). This work presents the development of an alternative source of resveratrol with possible applications in pharmaceutical, nutraceutical and food industry. (C) 2012 Elsevier Ltd. All rights reserved.
Keywords:Resveratrol;OptForce;Malonyl CoA;Stoichiometric-based modeling;Metabolic engineering;Synthetic biology