Applied Microbiology and Biotechnology

, Volume 93, Issue 5, pp 2063–2073

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

Authors

  • Brett A. Boghigian
    • Department of Chemical and Biological Engineering, Science and Technology CenterTufts University
  • John Armando
    • Department of Chemical and Biological Engineering, Science and Technology CenterTufts University
  • Daniel Salas
    • Department of Chemical and Biological Engineering, Science and Technology CenterTufts University
    • Department of Chemical and Biological Engineering, Science and Technology CenterTufts University
Applied genetics and molecular biotechnology

DOI: 10.1007/s00253-011-3725-1

Cite this article as:
Boghigian, B.A., Armando, J., Salas, D. et al. Appl Microbiol Biotechnol (2012) 93: 2063. doi:10.1007/s00253-011-3725-1

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

TaxolTaxadieneTaxadiene synthaseOver-expressionE. coliHeterologous biosynthesisMetabolic engineering

Copyright information

© Springer-Verlag 2011