Multi-steps microfiltration of micelles from fermentation of Streptomyces tsukubaensis and its impact on proteins retention and tacrolimus yield

This study reports the application of microfiltration Streptomyces tsukubaensis micelles from fermentation broths, for tacrolimus recovery, investigating the use of a new multi-step microfiltration approach. Equal volumes of acetone were added to the fermented broth, and the resultant mixture was processed through multi-step microfiltration at 26 °C in a pressurized chamber, with operational pressures of 1 bar and 2 bar, using membranes with pore sizes of 0.22 μm and 3.0 μm. The permeate was recirculated, configuring ten steps of operation using the same membrane. The analysis of micelles microfiltration focused on the influence of multi-step processes on permeate flow and time steps, allowing exploration of pore blocking models. The cake filtration mechanism was identified as predominant for global filtration. The study achieved a 97 % micelles rejection rate in ten steps with a 3.0 μm pore membrane at 1 bar. Protein retention was also studied, showing a final retention rate of 60 %, with 40 % of proteins in the final permeate. This multi-step filtration process acts as microfiltration for micelles and ultrafiltration for proteins, improving tacrolimus purity. However, the tacrolimus yield was reduced by 9 %, attributed to increased tacrolimus adsorption on the gel/cake layer surface rather than steric factors.