Abstract:Recent rapid developments of synthetic biology and genome sequencing technology opened new possibilities for the discovery and development of microbial natural products. However, a majority of natural products are difficult to access because many microorganisms cannot be cultured, or are difficult to be genetically manipulated. Heterologous expression of biosynthetic gene clusters (BGCs) for natural products in well-characterized hosts provides an alternative way for the discovery of natural products or improvement of their production. However, the success of this strategy hinges upon the cloning and refactoring and/or optimization of large gene clusters. CRISPR/Cas system greatly boosts the development of cloning and refactoring large gene clusters, and promotes the discovery of natural products from microorganisms. In this review, we summarized the recent advances in strategies for gene cluster cloning and refactoring based on CRISPR/Cas system, and discussed the application of related technologies in the discovery and development of natural products and their significance.
