Heterologous Natural Product Biosynthesis for Therapeutic Applications: Erythromycin Diversification

The Pfeifer Research Group

Erythromycin diversification

The experimetal results for Erythromycin diversification

The Pfeifer research group is interested in establishing the production of the antibiotic erythromycin, studying its altered antibiotic activity, and identifying new antibiotic compounds.

Overview

This work stems from our interest in establishing the production of the antibiotic erythromycin.  The biosynthetic process for erythromycin is complex, which on one hand complicates our engineering efforts but also offers the opportunity for multiple forms of compound variation through selectively altering facets of the biosynthetic process.  For example, we have recently begun varying the glycosylation patterns associated with erythromycin.  Importantly, by doing so, we have seen altered antibiotic activity.  In the future, we plan to exploit this diversification platform to greatly expand the chemical space associated with erythromycin for the purpose of identifying new antibiotic compounds.

Resulting Publications

  • M. Jiang, H. Zhang, S. Park, Y. Li, B.A. Pfeifer. ‘Deoxysugar Pathway Interchange for Erythromycin Analogues Heterologously Produced through E. coliMetabolic Engineering 20:92-100 (2013)
  • G. Zhang, Y. Li, L. Fang, B.A. Pfeifer. ‘Tailoring Pathway Modularity in the Biosynthesis of Erythromycin Analogs Heterologously Engineered in E. coliScience Advances 1(4): e1500077 (2015)

Students on this Projects

  • Guojian Zhang (Postdoctoral Associate)
  • Lei Fang (PhD, conferred Summer 2017)