Improvement of FK506 production by synthetic biology approaches.
Synthetic biology has been applied to direct improvement of valuable metabolite productions. Tacrolimus (FK506), a clinically used immunosuppressive agent isolated from many Streptomyces, is produced by fermentation in industry. Here we chose FK506 as an example to review recent progress in improving FK506 production, including enhancing transcription levels of biosynthetic genes, accelerating post-translational modification levels of biosynthetic enzymes, increasing activities of rate limiting enzymes, and rational supplement of limited precursors. FK506 production was increased from 25 % to sevenfold by these synthetic biology approaches.
Hangzhou Zhongmei Huadong Pharmaceutical Co. Ltd, Hangzhou, 310011, Zhejiang, China.
Li-Feng
LF
Fu
College of Life Sciences, Zhejiang University, 866 Yuhangtang Rd, Hangzhou, 310058, Zhejiang, China.
Yang
Y
Tao
Hangzhou Zhongmei Huadong Pharmaceutical Co. Ltd, Hangzhou, 310011, Zhejiang, China.
Mei-Ying
MY
Jin
College of Life Sciences, Zhejiang University, 866 Yuhangtang Rd, Hangzhou, 310058, Zhejiang, China. jianghuisioc@zju.edu.cn.
Hui
H
Jiang
D001426:Bacterial Proteins / Q000378:metabolism; D058615:Synthetic Biology / Q000379:methods*; D016559:Tacrolimus / Q000378:metabolism*; D017855:Transferases (Other Substituted Phosphate Groups) / Q000378:metabolism
D001426:Bacterial Proteins; C082662:phosphopantetheinyl transferase; D017855:Transferases (Other Substituted Phosphate Groups); D016559:Tacrolimus
Biosynthesis; FK506; Phosphopantetheinyl transferase; Regulator; Synthetic biology