title: Novel production of terpenoids in Escherichia coli and activities against breast cancer cell lines.
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.
authors.affiliation: Department of Biological Sciences, University of the Sciences, 600 South Forty-Third Street, Philadelphia, PA, 19104, USA, sgupta@mail.usciences.edu.
authors.forename: Shweta
authors.initials: S
authors.lastname: Gupta
authors.forename: Melissa G
authors.initials: MG
authors.lastname: Marko
authors.forename: Vandana A
authors.initials: VA
authors.lastname: Miller
authors.forename: Frederick T
authors.initials: FT
authors.lastname: Schaefer
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Anthony
authors.forename: John R
authors.initials: JR
authors.lastname: Porter
mesh_terms: D000970:Antineoplastic Agents / Q000378:metabolism* / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D053138:Cyclohexenes / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D045782:Hemiterpenes / Q000378:metabolism; D006801:Humans; D000077222:Limonene; D060847:Metabolic Engineering; D009943:Organophosphorus Compounds / Q000378:metabolism; D013729:Terpenes / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D053138:Cyclohexenes; D045782:Hemiterpenes; D009943:Organophosphorus Compounds; D013729:Terpenes; C004809:isopentenyl pyrophosphate; D000077222:Limonene