Heterologous Natural Product Biosynthesis for Therapeutic Applications: Erythromycin Production

The Pfeifer Research Group

Schematic for Erythromycin production

Schematic for Erythromycin production

The Pfeifer research group engineers the biosynthesis of complex natural product small molecules through an approach termed heterologous biosynthesis, in which a surrogate microbial host is utilized to access the compound of interest.

Overview

This project focuses on the microbial production of therapeutic small molecules using the tools of molecular biology and cellular design.  Students will learn the basics of biology and how it can be engineered for unique applications.  In this case, target compounds possess therapeutic value.  A prime example focused upon in the Pfeifer group is the production of the antibiotic erythromycin using Escherichia coli as a host.  Effectively, this is a chemical reaction within the confines of a biological cell.  As such, the basics and tools of biology are needed to influence and diversify production.

Resulting Publications

  • M. Jiang, H. Zhang, B.A. Pfeifer. ‘The Logic, Experimental Steps, and Potential of Heterologous Natural Product Biosynthesis Featuring the Complex Antibiotic Erythromycin A Produced through E. coliJournal of Visualized Experiments (71):e4346 (2013)
  • M. Jiang, L. Fang, B.A. Pfeifer. ‘Improved Heterologous Erythromycin A Production through Expression Plasmid Redesign’ Biotechnology Progress 29(4):862-9 (2013)
  • M. Jiang, B.A. Pfeifer. ‘Metabolic and Pathway Engineering to Influence Native and Altered Erythromycin Production through E. coliMetabolic Engineering 19:42-9 (2013)
  • L. Fang, H. Zhang, M. Osburne, B.A. Pfeifer. ‘The Continuing Development of E. coli as a Heterologous Host for Complex Natural Product Biosynthesis’ Methods in Molecular Biology 1401:121-34 (2016)

Students on this Projects

  • Lei Fang (PhD, conferred Summer 2017)
  • Dongwon Park (PhD)
  • Kaiwen Bao (MS, conferred Summer 2017)