Application of CRISPR/Cas9 Gene Editing System in Obtaining Natural Products in Actinomycetes

As important source of clinical drugs, the natural products in actinomycetes and their derivatives have been developed on a large scale and used in clinical practice. In order to achieve efficient synthesis of active natural products, structural derivation of new natural products, and targeted mining of unknown natural products, researches mainly focus on the biosynthetic gene clusters from actinomycetes, which should be rationally engineered by advanced biotechnology. CRISPR/Cas, which represents the clustered regularly interspaced short palindromic repeats and the associated protein, is an adaptive immune system developed by some bacteria and archaea in the long-term natural evolution process to resist the invasion of foreign genetic materials. As a representative of gene editing system, the clustered regularly interspaced short palindromic repeats and the associated protein 9 (CRISPR/Cas9) has been widely used in the targeted editing of deoxyribonucleic acid (DNA) fragments, which provides unlimited possibilities for the development of biotechnology. This paper reviews the application of the CRISPR/Cas9 system in the genetic manipulation of actinomycetes, including the recent research progress in capture, editing and reconstruction of gene clusters, in situ homologous recombination and metabolic regulation, which involves the novel CRISPR/Cas9-mediated gene editing methods and the representative successful cases. This paper will provide valuable information for the efficient use of CRISPR/Cas9 to obtain natural products in actinomycetes.