Agave salmiana syrup improves the production of recombinant human interleukin-2 in Escherichia coli

The expression of heterologous proteins in Escherichia coli is strongly affected by the type of carbon source used. In this work, the expression of a synthetic codon-optimized gene of human interleukin-2 in E. coli BL21-SI, carrying plasmid pET12a-hIL2 is presented. Glucose, fructose or Agave syrup from Agave salmiana, were used as carbon sources for production of recombinant human IL-2 (rhIL-2) in 1.5-L bioreactor aerobic cultures using mineral medium. Codon optimization of the native hIL-2 gene eliminated the presence of 35 rare codons for E. coli, and improved the codon usage up to 76% compared with the native gene sequence. Cultures using 10 g/L glucose showed the lowest production of rhIL-2, and in contrast, cultures using fructose improved the production of rhIL-2 1.9-times. The utilization of fructose from Agave syrup enhanced the rhIL-2 production 3.9-times, reaching 103.42±6.61 mgIL-2/L. The specific rhIL-2 production rate (5.52±0.33 mgIL-2/gDCW·h) using Agave syrup was also the highest. These results indicate that Agave syrup stimulates the production of rhIL-2 and it is an inexpensive alternative carbon source. This research abilities the potential use the Agaves to produce alternative and valuable biotechnological products instead the alcoholic beverages.

Keywords: codon optimization, fructose, NaCl inducer, recombinant protein, synthetic gene.