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

Publisher: Springer International Country of Publication: Germany NLM ID: 8406612 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-0614 (Electronic) Linking ISSN: 01757598 NLM ISO Abbreviation: Appl Microbiol Biotechnol Subsets: MEDLINE

Original Publication: Berlin ; New York : Springer International, c1984-

Gene Expression* ; Metabolic Engineering*; Alkenes/*metabolism ; Diterpenes/*metabolism ; Escherichia coli/*genetics ; Escherichia coli/*metabolism; Computational Biology/methods ; Metabolic Networks and Pathways/genetics

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.

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R01 GM085323 United States GM NIGMS NIH HHS; GM085323 United States GM NIGMS NIH HHS

0 (Alkenes)
0 (Diterpenes)
0 (taxa-4(5),11(12)diene)

Date Created: 20111130 Date Completed: 20120606 Latest Revision: 20230207

20250114

PMC9896017

10.1007/s00253-011-3725-1

22124721