Elucidating novel regulatory mechanisms of antimycin-type depsipeptide biosynthesis

点击翻译按钮获取中文摘要

Soil bacteria, namely streptomycetes, produce more than half of all drugs used in human medicine, ranging from antibiotics to cure infectious disease as well as drugs to treat cancer and enable organ transplantation. Only about one-tenth of the bacterial genes that enable the production of these compounds are expressed in the laboratory. In other words, the global pharmaceutical industry is based on ~10% of the biochemical diversity it could be. A lack of knowledge as to how bacteria control the production of these potentially useful chemicals is one of the most significant challenges faced by the field of drug discovery and fundamental advances in this area could result in the discovery and development of a multitude of new therapeutics for a wide range of diseases. We have identified a novel regulatory protein (called a 'transcription factor') that controls the expression of a subset of genes in the pathway that makes compounds with promising activity as anticancer agents and treatments for the neurodegenerative conditions, Alzheimer's and Parkinson's diseases. Treating these age-related diseases with a small molecule is very attractive and has the potential to decrease the mortality and improve the quality of life of patients. Our ultimate goal is elucidate other regulators of this pathway and understand in detail how production of these molecules is controlled so that we may engineer their overproduction. Doing so will result in knowledge-based improvements in yield and the approaches we take and tools we make could be used in the same with for other potential drugs, possibly making them less expensive and more widely available.