Streptomyces tsukubaensis Fermentation Using Brazil Nut Oil to Enhance Tacrolimus Production

Introduction: Tacrolimus is a medication mainly used as immunosuppressant, but also plays as an important role in the treatment of dermathoses and eye diseases. It is a secondary metabolite produced during fermentation from Streptomyces tsukubaensis. Investigations have been conducted in order to enhance the tacrolimus production, since it is the greatest industrial bottleneck related to this process. Some strategies have been adopted in order to solve this problem, such as the usage of a genetically modified bacteria and changes in the exogeneous feeding, and providing vegetable oils as nutrient sources. The present study has investigated the influence of the Brazil nut (Bertholletia excelsa) oil as a carbon source in the fermentation. Materials and Methods: The fermentative process was conducted in an orbital shaker at 28oC and 130 rpm during 168 hours. The amount of produced tacrolimus was quantified using HPLC. The sugars and proteins in the medium were measured using the Somogyi-Nelson and Bradford methods, respectively. Results: According to the results of the present study, a linearity was observed between the amount of consumed sugars and the produced proteins. The highest tacrolimus production was achieved at 96 hours (41.67 mg.L-1), and the biomass production along the fermentation was low. Conclusions: The use of Brazil nut oil as a carbon source in the fermentation using Streptomyces tsukubaensis was successful, since it increased the tacrolimus production. This point is an advantage of using this vegetable oil compared to traditional sugars.

Keywords:

Tacrolimus Production , Vegetable oils , Brazil Nut Oil , Batch fermentation , Biotechnology