Abstract |
Metabolic engineering of heterologous pathways has allowed the production of therapeutically important compounds in microbial systems. Here, we report the engineering of a monoterpenoid biosynthetic pathway into Escherichia coli. Five genes encoding sequential enzymes for perillyl alcohol biosynthesis from the precursors isopentenyl pyrophosphate ( IPP) and dimethylallyl pyrophosphate ( DMAPP) were engineered into E. coli. Expression of these genes allowed the production of the intermediate limonene, but the downstream monoterpenoid, perillyl alcohol, was not detected. A new compound was detected but could not be identified based on the data obtained. Only 1.6 μg/ml of the compound was being produced from the engineered E. coli strain, but, when these cultures were fed limonene as a substrate, the production was nearly 250 μg/ml. This unknown compound inhibited the cell proliferation of MCF-7 and MDA-MB-231 breast cancer cells in 48-h treatment experiments. This compound may have potential benefits in breast cancer treatment. This is the first report showing the production of a monoterpenoid in engineered E. coli and its antiproliferative effects in breast cancer cells.
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Authors | Shweta Gupta, Melissa G Marko, Vandana A Miller, Frederick T Schaefer, Jennifer R Anthony, John R Porter |
Journal | Applied biochemistry and biotechnology
(Appl Biochem Biotechnol)
Vol. 175
Issue 5
Pg. 2319-31
(Mar 2015)
ISSN: 1559-0291 [Electronic] United States |
PMID | 25484192
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents
- Cyclohexenes
- Hemiterpenes
- Organophosphorus Compounds
- Terpenes
- isopentenyl pyrophosphate
- Limonene
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Topics |
- Antineoplastic Agents
(metabolism, pharmacology)
- Breast Neoplasms
(drug therapy, physiopathology)
- Cell Line, Tumor
- Cell Proliferation
(drug effects)
- Cyclohexenes
(metabolism)
- Escherichia coli
(genetics, metabolism)
- Female
- Hemiterpenes
(metabolism)
- Humans
- Limonene
- Metabolic Engineering
- Organophosphorus Compounds
(metabolism)
- Terpenes
(metabolism, pharmacology)
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