Activation of Silent Natural Product Biosynthetic Gene Clusters Using Synthetic Biology Tools

Natural products are a major source of highly valuable bioactive compounds. However, most of the biosynthetic gene clusters (BGCs) encoding natural products are either silent or poorly expressed under the laboratory conditions. To activate silent BGCs as well as to make the natural product discovery process more efficient, many synthetic biology tools have been developed in the past decade. This article will provide a comprehensive and critical review of the synthetic biology strategies and tools developed for activating silent BGCs for discovery of natural products, which can be grouped into two categories: activation of silent BGCs in native hosts and activation of silent BGCs in heterologous hosts. A few successful examples will also be highlighted.