TY - JOUR
T1 - Redirecting carbon flux into malonyl-CoA to improve resveratrol titers
T2 - Proof of concept for genetic interventions predicted by OptForce computational framework
AU - Bhan, Namita
AU - Xu, Peng
AU - Khalidi, Omar
AU - Koffas, Mattheos A.G.
N1 - Funding Information:
We acknowledge the financial support from the National Science Foundation awarded to Dr. M.A.G. Koffas.
PY - 2013/11/5
Y1 - 2013/11/5
N2 - 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.
AB - 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.
KW - Malonyl CoA
KW - Metabolic engineering
KW - OptForce
KW - Resveratrol
KW - Stoichiometric-based modeling
KW - Synthetic biology
UR - http://www.scopus.com/inward/record.url?scp=84879190343&partnerID=8YFLogxK
U2 - 10.1016/j.ces.2012.10.009
DO - 10.1016/j.ces.2012.10.009
M3 - 文章
AN - SCOPUS:84879190343
SN - 0009-2509
VL - 103
SP - 109
EP - 114
JO - Chemical Engineering Science
JF - Chemical Engineering Science
ER -