Complete biosynthesis of erythromycin A and designed analogs using E. coli as a heterologous host

Chem Biol. 2010 Nov 24;17(11):1232-40. doi: 10.1016/j.chembiol.2010.09.013.

Abstract

Erythromycin A is a potent antibiotic long-recognized as a therapeutic option for bacterial infections. The soil-dwelling bacterium Saccharopolyspora erythraea natively produces erythromycin A from a 55 kb gene cluster composed of three large polyketide synthase genes (each ~10 kb) and 17 additional genes responsible for deoxysugar biosynthesis, macrolide tailoring, and resistance. In this study, the erythromycin A gene cluster was systematically transferred from S. erythraea to E. coli for reconstituted biosynthesis, with titers reaching 10 mg/l. Polyketide biosynthesis was then modified to allow the production of two erythromycin analogs. Success establishes E. coli as a viable option for the heterologous production of erythromycin A and more broadly as a platform for the directed production of erythromycin analogs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / biosynthesis*
  • Anti-Bacterial Agents / chemistry
  • Erythromycin / analogs & derivatives
  • Erythromycin / biosynthesis*
  • Escherichia coli / genetics
  • Escherichia coli / metabolism*
  • Mass Spectrometry
  • Multigene Family
  • Plasmids / metabolism
  • Polyketide Synthases / genetics
  • Saccharopolyspora / metabolism

Substances

  • Anti-Bacterial Agents
  • Erythromycin
  • Polyketide Synthases