Linnea Verhey-Henke
Pronouns: she/her
Research Mentor(s): Filipa Barroso Pereira
Research Mentor School/College/Department: Life Sciences Institute, University of Michigan / Other
Program: UROP
Session: Session 3 (11:00am – 11:50am)
Authors: Linnea Verhey-Henke, Filipa Barroso Pereira, Morgan McCauley, David H. Sherman
Abstract
Natural products are an invaluable source of pharmaceutical compounds. Traditional bioactivity-guided isolation of natural products was able to successfully identify Concanamycin A as a modulator of MHC-1 regulation in HIV-infected cells. Although this is excellent news, it comes at a price. The molecule costs >$695/mg making it unattainable for further chemical modification studies and production into a cost-effective drug. Concanamycin A is naturally produced by Streptomyces at low titters. This project focuses on the improved production of Concanamycin A through metabolic engineering and growth optimisation. First, we overexpress key pathway regulators in a known Concanamycin A producer strain. Next, by screening multiple growth conditions we were able to produce the target metabolite at concentrations of 500mg/L. Optimizing extraction and purification protocols we are now able to isolate & < 93mg/L of pure Concanamycin A. Using the developed approaches, we aim to accelerate the discovery and production of novel compounds, in sufficient quantities to support medicinal chemistry studies.
