Applied Microbiology and Biotechnology

, Volume 93, Issue 5, pp 2063–2073 | Cite as

Computational identification of gene over-expression targets for metabolic engineering of taxadiene production

  • Brett A. Boghigian
  • John Armando
  • Daniel Salas
  • Blaine A. Pfeifer
Applied genetics and molecular biotechnology

Abstract

Taxadiene is the first dedicated intermediate in the biosynthetic pathway of the anticancer compound Taxol. Recent studies have taken advantage of heterologous hosts to produce taxadiene and other isoprenoid compounds, and such ventures now offer research opportunities that take advantage of the engineering tools associated with the surrogate host. In this study, metabolic engineering was applied in the context of over-expression targets predicted to improve taxadiene production. Identified targets included genes both within and outside of the isoprenoid precursor pathway. These targets were then tested for experimental over-expression in a heterologous Escherichia coli host designed to support isoprenoid biosynthesis. Results confirmed the computationally predicted improvements and indicated a synergy between targets within the expected isoprenoid precursor pathway and those outside this pathway. The presented algorithm is broadly applicable to other host systems and/or product choices.

Keywords

Taxol Taxadiene Taxadiene synthase Over-expression E. coli Heterologous biosynthesis Metabolic engineering 

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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Brett A. Boghigian
    • 1
  • John Armando
    • 1
  • Daniel Salas
    • 1
  • Blaine A. Pfeifer
    • 1
  1. 1.Department of Chemical and Biological Engineering, Science and Technology CenterTufts UniversityMedfordUSA

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