Natural products and their related derivatives play a significant role in drug discovery and have been the inspiration for the design of numerous synthetic bioactive compounds. With recent advances in molecular biology, numerous engineering tools and strategies were established to accelerate natural product synthesis in both academic and industrial settings. However, many obstacles in natural product biosynthesis still exist. For example, the native pathways are not appropriate for research or production; the key enzymes do not have enough activity; the native hosts are not suitable for high-level production. Emerging molecular biology tools and strategies have been developed to not only improve natural product titers but also generate novel bioactive compounds. In this review, we will discuss these emerging molecular biology tools and strategies at three main levels: enzyme level, pathway level, and genome level, and highlight their applications in natural product discovery and development.
We gratefully acknowledge financial support from the National Institutes of Health (GM077596 and AI144967 to H.Z.), the A*STAR Visiting Investigator Program (H.Z.), and the National Research Foundation, Singapore (NRF2017NRF-CRP001-044) (E.A.).