Fig. 4.

The role of cofactors in the biosynthesis of resveratrol. a Metabolic network graph connecting metabolites, genes, and reactions with fluxes during resveratrol biosynthesis. The highlighted circles represent metabolites with high connectivity in the model. ACCOA acetyl-CoA, AKG 2-oxoglutarate, GLU glutamate, PI phosphate, PPI diphosphate. b Cofactors that participated in resveratrol biosynthesis pathway based on GSMM. Three modules represent the shikimate pathway (purple), phenylpropanoid pathway (blue), and the malonyl-CoA synthesis pathway (green), respectively. Dashed arrows indicate the pathways that are not listed in detail. Red arrows indicate the flow changes in response to increasing resveratrol production from 0.0073 to 0.02 mmol/gDW/h. Green/red circles: metabolites in cytosol/mitochondria, orange circles: cofactors. PPP pathway pentose phosphate pathway, EMP pathway glycolysis pathway, e4p d-erythrose 4-phosphate, pep phosphoenol pyruvate, 3ddah7p 2-dehydro-3-deoxy-d-arabino-heptonate 7-phosphate, dqt 3-dehydroquinate, dhsk 3-dehydroshikimate, sme shikimate, sme3p shikimate 3-phosphate, 3psme 5-O-(1-carboxyvinyl)-3-phosphoshikimate, chor chorismate, phen prephenate, 4hppyr 4-hydroxyphenylpyruvate, ty l-tyrosine, couma 4-coumarate, ppyr phenylpyruvate, phe l-phenylalanine, cinnm trans-cinnamate, cincoa cinnamoyl-CoA, 4cmcoa p-coumaroyl-CoA, malcoa malonyl-CoA, 2mlaacoa 2-methylacetoacetyl-CoA, ile l-isoleucine, pyr pyruvate, micit methylisocitrate, lac (R)-lactate, cit citrate, acacp acetyl-[acyl-carrier protein], aaccoa acetoacetyl-CoA, nag6p N-acetyl-d-glucosamine 6-phosphate, hmgcoa (S)-3-hydroxy-3-methylglutaryl-CoA, RES resveratrol