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.
Keywords: Biosynthesis; FK506; Phosphopantetheinyl transferase; Regulator; Synthetic biology.