Chemical biology of tetracycline antibiotics

For more than half a century, tetracycline antibiotics have been used to treat infectious disease. However, what once used to be a commonly prescribed family of antibiotics has now decreased in effectiveness due to wide-spread bacterial resistance. The chemical scaffold of the tetracyclines is a versatile and modifiable structure that is able to interact with many cellular targets. The recent availability of detailed molecular interactions between tetracycline and its cellular targets, along with an understanding of the tetracycline biosynthetic pathway, has provided us with a unique opportunity to usher in a new era of rational drug design. Herein we discuss recent findings that have clarified the mode of action and the biosynthetic pathway of tetracyclines and that have shed light on the chemical biology of tetracycline antibiotics.