Engineering of modular polyketide synthases (PKS) can create natural product derivatives, however, de novo generation of defined structures with good productivity remains challenging. Here, the authors employ a gene conversion-driven strategy to reprogram the cinnamomycin biosynthetic gene cluster, successfully generating a series of new macrolides with designed structural features and highlighting the role of the KS domain in extender unit proofreading.
- Wenzheng Jin
- Jiaming Tu
- Yijun Chen
