Tetracycline natural products: discovery, biosynthesis and engineering

Tetracycline (TC) natural products possess a variety of remarkable bioactivities and diverse structures. They are an important and fertile source for developing novel drugs. As one of the most successful drug families, TC antibiotics have been in clinical use for over seven decades, and continue to make an important contribution to human health nowadays. To date, studies on TC natural products and their biosynthesis have revealed numerous novel biochemical mechanisms and regulatory elements, which facilitates the rational metabolic engineering studies for generating novel bioactive TC analogs and inspires the development of new synthetic biology tools. In this review, we provide a comprehensive overview on the discovery, biosynthesis, and engineering of the existing TC natural products. These analyses will be of great value for the discovery, design and development of novel TC drugs in the future.

Automated summary

Tetracycline is a class of natural products with diverse bioactivities and structures, serving as a valuable source for developing novel drugs. As one of the most successful antibiotic families, tetracyclines have been widely used in clinical practice for over seven decades, making significant contributions to human health. Studies have revealed novel biochemical mechanisms and regulatory elements underlying the biosynthesis of tetracycline natural products, enabling rational metabolic engineering for generating bioactive analogs and inspiring the development of synthetic biology tools.