Preparative ion exchange purification of capreomycin from fermentation broth produced by Streptomyces capreolus.

Capreomycin (CMN) is a second-line aminoglycoside antibiotic for treating multi-drug resistant tuberculosis. Produced as a complex broth in microbial bioreactors, the downstream purification of CMN traditionally requires multiple steps. Current work aims to purify CMN as mixed isomers in a single step by preparative macroporous cation-exchange chromatography in >98% purity in >90% yield. Selection of the adsorbent best suited for CMN purification was guided by modeling the molecular interactions, followed by wet-lab static and dynamic adsorption studies that validated the simulation results. Among the evaluated adsorbents (both weak and strong cation resins), the weak cationic Macro-Prep CM showed a favorable combination of selective binding and elution of CMN. Solute loading and elution conditions were further optimized to produce the desired quality of CMN. This single-step method was integrated with a continuous simulated bed reverse-phase desalting chromatography to produce 99% pure salt-free CMN. The proposed method provided productivity of about 2 g product/L resin/h of CMN on Macro-Prep CM; and 0.7 g product/L adsorbent/h on SMB. The study provides for a robust and scalable process for the industrial-scale production of purified capreomycin. [ABSTRACT FROM AUTHOR]