Naringenin is one of the most relevant polyphenols due to its benefits to human health. Different studies have shown that naringenin may reduce lipid accumulation in the body, has antiviral activity in the SARV-COV-2 and hepatitis C viruses, and anti-inflammatory activity in cancer. Naringenin is commonly produced by chemical synthesis and plant extraction. Both processes have low yields and are not environmentally friendly. Therefore, the design and engineering of microorganisms has been implemented as an alternative way to produce naringenin. Heterologous naringenin production in Escherichia coli involves four enzymes: PAL, 4CL, CHS and CHI, and three malonyl-CoA molecules. In different studies, malonyl-CoA has been reported as the primary precursor for naringenin. To improve naringenin production, it is necessary to increase the flux of malonyl-CoA into the naringenin pathway. One of the strategies to increase the flux of malonyl-CoA is by controlling the oxygen transfer. To evaluate the effect of oxygen, an in-silico study was developed, implementing the phenotype phase plane. At higher concentrations of oxygen and glucose, the highest flux of malonyl-CoA to the naringenin pathway was obtained since acetyl-CoA is mainly converted to malonyl-CoA and it is not used by the TCA cycle. To validate the results in silico, naringenin production was evaluated in vitro at different aeration rates. At 18 hours of naringenin production, the yield of naringenin (mg naringenin per gram of biomass) at 50 rpm was 11.47±0.24 and 3.51±0.01 at 300 rpm. Thus, it was demonstrated that oxygen transfer does have an impact on heterologous naringenin production.

Evaluation of oxygen transfer in heterologous production of naringenin in Escherichia coli from previous designed pathway

ACS Fall 2021

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