The ASPIRE Path in Molecular Medicine

Biosynthetic gene clusters (BGC) are groups of genes that encode large molecules that are bioactive called natural products. These natural products can be antibacterial, antifungal, antitumor etc. Streptomyces are a genus of bacteria that have comparatively large genome sizes and often contain many BGC, however many remain cryptic, or not expressed in a laboratory setting. With a global increase in antibiotic resistance, there is immense pressure to find novel compounds that can be used medicinally. To induce transcription of BGC and synthesis of natural products, small molecule elicitors can be used to cause global changes in the transcriptome and metabolome. In some species of Streptomyces, JadR2, a regulatory gene in the jadomycin BGC, can regulate expression of the cluster in the presence of other antibiotics such as chloramphenicol. A predicted homolog of JadR2 was found in the g-butyrolactone BGC in Streptomyces exfoliatus . g-butyrolactone is known to act as a small molecule elicitor in other species. My project is focused on exploring the role of the JadR2 homolog in expression or repression of g-butyrolactone in the presence of chloramphenicol. I am interested in characterizing the role of these genes as well as the ways in which global metabolism is regulated.