The collinearity between the architectures of modular polyketide synthases (PKS) and the structures of their polyketide products would suggest these biosynthetic machineries are excellent platforms for designer biosynthesis, yet reliable strategies to reprogram these assembly lines without diminishing their activities have not been identified. Here, the authors demonstrate the reprogramming of the mediomycin PKS without significant loss of productivity, and reconstruct an inaccessible drug lead of the fibrinogen receptor, tetrafibricin, at 82 mg/L yield.
- Kei Kudo
- Takuya Hashimoto
- Kazuo Shin-ya