Vancomycin Group Antibiotics: from an Understanding of Biosynthesis and Resistance to Improving upon Nature’s Design

Title of Document: VANCOMYCIN GROUP ANTIBIOTICS: FROM AN UNDERSTANDING OF BIOSYNTHESIS AND RESISTANCE TO IMPROVING UPON NATURE’S DESIGN James J. Gorman Master of Life Science with a concentration in chemistry 2008 Directed By: Dr. Philip DeShong, Organic Chemistry Methicillin-resistant Staphylococcus aureus (MRSA) infections are not simply relegated to healthcare associated event anymore. News reports abound with the tales of many community acquired MRSA infections that lead to serious hospitalization and all too often death. The drug of last resort for these infections is vancomycin; a natural product obtained from the soil bacteria Amycolatopsis orientalis. An increasing amount of research has been devoted to understanding the regulatory mechanism controlling vancomycin production namely the role of glucose, oxygen, and an StrR-like regulator. A more in-depth understanding of vancomycin-type biosynthetic gene clusters has revealed key incites into vancomycin production. Vancomycin-resistant strains are becoming more prevalent necessitating the development of new alternatives that build off of the vancomycin-core like oritavancin. Knowledge of resistance mechanisms and structure-activity relationships has paved the way for this burgeoning success. VANCOMYCIN GROUP ANTIBIOTICS: FROM AN UNDERSTANDING OF BIOSYNTHESIS AND RESISTANCE TO IMPROVING UPON NATURE’S DESIGN