Metabolic engineering of Streptomyces to enhance the synthesis of valuable natural products

The mycelial bacterium Streptomyces is a workhorse for producing natural products, serving as a key source of drugs and other valuable chemicals. However, its complicated life cycle, silent biosynthetic gene clusters (BGCs), and poorly characterized metabolic mechanisms limit efficient production of natural products. Therefore, a metabolic engineering strategy, including traditional and emerging tools from different disciplines, was developed to further enhance natural product synthesis by Streptomyces. Here, current trends in systems metabolic engineering, including tools and strategies, are reviewed. Particularly, this review focuses on recent developments in the selection of methods for regulating the Streptomyces life cycle, strategies for the activation of silent gene clusters, and the exploration of regulatory mechanisms governing antibiotic production. Finally, future challenges and prospects are discussed.