Escherichia coli K12f-pACLYC has a high capability for growth and lycopene production when using fructose as carbon source and the transcription of genes involved was compared in glucose-grown and fructose-grown cells. Escherichia coli K12f-pACLYC was grown on 10 g fructose l(-1) and reached 4.6 g DCW l(-1) with lycopene at 192 mg g DCW-1, values that are 3-fold and 7-fold higher than when growing on glucose. Gene transcription profiles of fructose-grown and glucose-grown cells were compared. 384 differentially expressed genes (DEGs) with fold changes aeyen4 were identified, and the transcription of genes involved in fructose uptake and metabolism, pyruvate catabolism, tricarboxylic acid cycle and oxidative phosphorylation varied significantly. These changes enhanced the metabolic flux into the Embden-Meyerhof-Parnas pathway and the tricarboxylic acid cylcle and coupled to oxidative phosphorylation. These enhanced activities provide more precursors, cofactors and energy needed for growth lycopene production. The high capability of E. coli K12f-pACLYC for growth and lycopene production when growing on fructose is due to transcriptional regulation, and the relevant genes were identified.