An immunosuppressant tacrolimus-producing strain of Streptomyces sp. TST8 was isolated and developed by the TS corporation in Korea using the sequential adaptation of media containing tacrolimus (600-1600 mg/l). The aim of the tacrolimus sequential adaptation protocol was to select those cells with tacrolimus resistance and to reduce product inhibition of the tacrolimus-producing strain. The developed strains produced more tacrolimus than the original strain. In particular, the TST10 strain adapted in the medium containing 900 mg/l of tacrolimus produced 972 mg/l of tacrolimus in the final titer after 7 days of cultivation in a 5-l jar fermenter. This is the largest final titer of tacrolimus produced by a specific strain to date. Because the sequential adaptation protocol is limited by the solubility of tacrolimus in water, the final tacrolimus titer of TST11 adapted in the medium containing 1600 mg/l of tacrolimus was lower than that of TST10. The developed strains and the development method using sequential adaptation can facilitate the efficient and economical production of tacrolimus.
The immunosuppressant tacrolimus produced by Streptomyces sp. TST10 was purified in a process that included extraction, pre-adsorption using HP20 resin, adsorption using CG161M resin, and crystallization. In this study, the purification process using the adsorption resin CG161M was optimized by correlating tacrolimus yield with analogue load. One-step adsorption and two-step adsorption using CG161M can be applied selectively to the purification process, according to the analogue load of the input solution. We determined a correlation between the analogue load and the first adsorption yield in the two-step adsorption. We also observed yields according to the analogue loads in the one-step adsorption and the second adsorption of the two-step adsorption. As a result, the purification yields can be predicted by input conditions (analogue load). The purification strategy can be modified to achieve specific goals of purity, yield, and cost.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations鈥揷itations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.