Redirecting carbon flux into malonyl-CoA to improve resveratrol titers: Proof of concept for genetic interventions predicted by OptForce computational framework

摘要

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 (PGK), 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.