Team:British Columbia/Naringenin

Maintaining elevated production and activity levels of enzymes in an engineered biosynthetic pathway is a significant metabolic burden for the host cell. This burden is exacerbated when different enzymes within a biosynthetic pathway have varied or competing environmental and nutrient dependencies, like redox state 1, 2.

Through the expression of 6 exogenous genes, E. coli is able to convert glucose into kaempferol, a flavonol that acts as an antioxidant and has been reported to have anti-cancer properties 3, 4. Biosynthesis of kaempferol involves the conversion of tyrosine into p-coumaric acid, malonyl-CoA dependent production of the flavanone naringenin and subsequent functionalization into kaempferol 3-5.

This pathway was split into two biosynthetic modules, with naringenin acting as an intermediate that can be transferred between co-culture members. This co-culture design is especially effective in the context of kaempferol production as biosynthetic module 1 (naringenin biosynthesis) is malonyl-CoA dependant and biosynthetic module 2 (naringenin conversion into kaempferol) is NADPH dependant6.

Dividing these two functional enables the metabolic equilibrium within each strain to be optimized for the specific module, maximizing the efficiency of energy utilization by the cell.


  1. Zhang, H. and X. Wang, Modular co-culture engineering, a new approach for metabolic engineering. Metabolic Engineering, 2016. 37: p. 114-121.
  2. Zhang, H., et al., Engineering Escherichia coli coculture systems for the production of biochemical products. Proceedings of the National Academy of Sciences, 2015. 112(27): p. 8266.
  3. Duan, L., et al., Biosynthesis and engineering of kaempferol in Saccharomyces cerevisiae. Microbial Cell Factories, 2017. 16: p. 165.
  4. Jones, J.A., et al., Complete Biosynthesis of Anthocyanins Using E. coli Polycultures. mBio, 2017. 8(3).
  5. Ganesan, V., et al., Heterologous biosynthesis of natural product naringenin by co-culture engineering. Synthetic and Systems Biotechnology, 2017. 2(3): p. 236-242.
  6. Jones, J.A., et al., Experimental and computational optimization of an Escherichia coli co-culture for the efficient production of flavonoids. Metabolic Engineering, 2016. 35: p. 55-63.