Optimization of media and culture conditions for the production of tacrolimus by Streptomyces tsukubaensis in shake flask and fermenter level

Abstract

Abstract Goal of present research based on optimization of tacrolimus production by One-factor-at-a-time method and response surface methodology (RSM) using Streptomyces tsukubaensis NBRC 108819. Plackett–Burman Design was adopted for the selection of main nutrients inducing the production of tacrolimus. Out of 19 factors studied by Plackett–Burman Design, three variables (ammonium sulphate, yeast extract and 1, 2 propylene glycol) influenced the tacrolimus production most significantly. Thus in Central Composite Design the optimum concentrations of ammonium sulphate, yeast extract and 1, 2 propylene glycol were optimized for the maximum production of tacrolimus. The optimum medium composition for tacrolimus production was glucose (4 g/L), yeast extract (14.32 g/L), 1, 2 propylene glycol (1.49%), glycine (0.2 g/L) and ammonium sulphate (30 g/L). Optimized medium by statistical approach demonstrated the significant effect on tacrolimus production and increased it production from 205 ± 22.0 mg/L to 604 ± 54.6 mg/L in comparison to basal media. In addition optimized conditions were also used at bioreactor level to scale up the fermentation process in which tacrolimus production was attained 616 ± 52.2 mg/L after 168 h fermentation.