title: Computational identification of gene over-expression targets for metabolic engineering of taxadiene production.
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.
authors: Department of Chemical and Biological Engineering, Science and Technology Center, Tufts University, 4 Colby Street, Medford, MA 02155, USA.
authors: Brett A
authors: BA
authors: Boghigian
authors: John
authors: J
authors: Armando
authors: Daniel
authors: D
authors: Salas
authors: Blaine A
authors: BA
authors: Pfeifer
mesh_terms: D000475:Alkenes / Q000378:metabolism*; D019295:Computational Biology / Q000379:methods; D004224:Diterpenes / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism*; D015870:Gene Expression; D060847:Metabolic Engineering; D053858:Metabolic Networks and Pathways / Q000235:genetics
chemical_list: D000475:Alkenes; D004224:Diterpenes; C093125:taxa-4(5),11(12)diene