Strain development of Streptomyces sp. for tacrolimus production using sequential adaptation.
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.
Jung
Sangwon
S
Graduate Program of Bioengineering, Seoul National University, Seoul, Korea.
Moon
Sunghyun
S
Lee
Kyungsun
K
Park
Youn-Je
YJ
Yoon
Sewang
S
Yoo
Young Je
YJ
D000222:Adaptation, Physiological; D003470:Culture Media; D024881:Drug Resistance, Bacterial; D005285:Fermentation; D007166:Immunosuppressive Agents / Q000378:metabolism*; D007218:Industrial Microbiology; D007723:Korea; D008826:Microbial Sensitivity Tests; D013302:Streptomyces / Q000145:classification / Q000235:genetics / Q000302:isolation & purification* / Q000502:physiology; D016559:Tacrolimus / Q000378:metabolism*
D003470:Culture Media; D007166:Immunosuppressive Agents; D016559:Tacrolimus