Strain development of Streptomyces sp. for tacrolimus production using sequential adaptation

Area of Science:

• Microbiology
• Biotechnology
• Pharmacology

Background:

• Tacrolimus is a crucial immunosuppressant drug.
• Optimizing tacrolimus production is vital for its availability.
• Strain development is key to improving fermentation yields.

Purpose of the Study:

• To develop a high-yield tacrolimus-producing strain of Streptomyces sp.
• To investigate the efficacy of sequential adaptation for enhancing tacrolimus production.
• To overcome product inhibition in tacrolimus fermentation.

Main Methods:

• Isolation and development of Streptomyces sp. TST8.
• Sequential adaptation of the strain in media with increasing tacrolimus concentrations (600-1600 mg/l).
• Fermentation in a 5-l jar fermenter to determine tacrolimus final titer.

Main Results:

• Developed strains exhibited increased tacrolimus production compared to the original.
• Strain TST10, adapted in 900 mg/l tacrolimus, achieved a record final titer of 972 mg/l.
• Higher tacrolimus concentrations (1600 mg/l) showed reduced yields due to solubility limitations.

Conclusions:

• Sequential adaptation is an effective method for developing high-yield tacrolimus-producing strains.
• The developed strains and method facilitate efficient and economical tacrolimus production.
• Strain TST10 represents a significant advancement in tacrolimus fermentation technology.