Evolution inspired engineering of antibiotic biosynthesis enzymes

Abstract

Streptomyces soil bacteria are competent chemists that are able to produce thousands of chemically complex natural products. Key to the development of this rich source of metabolites appears to be an evolutionary pressure that promotes chemical diversity; new biosynthetic pathways are continuously being formed in these bacteria, which may result in the appearance of a novel bioactive compound that provides significant competitive advantage to the producing organism. In recent years, our work has focused on understanding how minor changes in the biosynthetic enzymes has led to drastically altered catalytic properties. We have generated chimeric proteins from functionally distinct homologous enzymes involved in the tailoring steps of related anthracycline and angucycline pathways, with the aim of creating novel catalysts. The work provides an opportunity for further protein engineering efforts for production of improved bioactive natural products.