Journal of Radiation Research and Radiation Processing ›› 2019, Vol. 37 ›› Issue (5): 6-050401-8.doi: 10.11889/j.1000-3436.2019.rrj.37.050401

• RADIATION TECHNOLOGY APPLICATION • Previous Articles     Next Articles

Breeding of tacrolimus high-producing strains by gamma-ray radiation and nitrosoguanidine mutagent

YAN Lingbin1(),ZHANG Wenzhou2,ZHANG Zhulan1(),ZHANG Yin1,QIU Guanrong1,WANG Desen1,LIAN Yunyang1()   

  1. 1. Fujian Provincial Key Laboratory of Screening for Novel Microbial Products, Fujian Institute of Microbiology, Fuzhou 350007, China
    2. Quanzhou Medical College, Quanzhou 362100, China
  • Received:2019-05-17 Revised:2019-07-02 Accepted:2019-07-02 Online:2019-10-20 Published:2019-10-15
  • Contact: Zhulan ZHANG,Yunyang LIAN;;
  • About author:YAN Lingbin (female) was born in January 1987, and graduated from Fuzhou University in 2012. Now she is a probationer professor in Fujian Institute of Microbiology, majoring in microbiology breeding. E-mail:
  • Supported by:
    Special Project of Public Welfare Research Institute of Fujian Province of China(2019R1005-8);Science and Technology Planning Project of Fuzhou City of China(2018-G-48);Science and Technology Planning Project of Fuqing City of China (2018(6) Fuqing City)


To enhance the tacrolimus fermentation titer of the production strain, original strains were treated using 60Co γ-ray radiation at a dose of 450 Gy and nitrosoguanidine mutagen (NTG) at a concentration of 3 mg/mL for 30 min when combined with a streptomycin and gentamycin resistance screening technique. A mutant strain named FIM-17-17 showed a 65% higher-yield tacrolimus than that of the original strain in a flask culture. The stability of the high-yield mutants and the effects of different resins (AB-8, D101, HT60, XAD16, HP20, and XDA-8) on the tacrolimus fermentation titer were investigated, and the optimized conditions of the mutant strain were tested in a 1-ton fermentation tank. The mutant strain FIM-17-17 showed high genetic stability. When 2% D101 resin was added to the culture medium, the tacrolimus titer increased by 29.8%, and the production of tacrolimus reached 1 319 μg/mL in the 1-ton fermentor. These results indicate that a tacrolimus high-producing strain can be obtained efficiently by compounding mutagenesis of 60Co γ-ray radiation and NTG.

Key words: Streptomyces, Tacrolimus, Fermentation, Radiation mutagenesis, Nitrosoguanidine mutagen(NTG)

CLC Number: 

  • TL99,TQ465.92