Computational identification of gene over-expression targets for metabolic engineering of taxadiene production |
| |
Authors: | Brett?A?Boghigian John?Armando Daniel?Salas Email author" target="_blank">Blaine?A?PfeiferEmail author |
| |
Institution: | (1) Department of Chemical and Biological Engineering, Science and Technology Center, Tufts University, 4 Colby Street, Medford, MA 02155, USA; |
| |
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: | |
本文献已被 PubMed SpringerLink 等数据库收录! |
|