title: Orthologs of the archaeal isopentenyl phosphate kinase regulate terpenoid production in plants.
abstract: Terpenoids, compounds found in all domains of life, represent the largest class of natural products with essential roles in their hosts. All terpenoids originate from the five-carbon building blocks, isopentenyl diphosphate (IPP) and its isomer dimethylallyl diphosphate (DMAPP), which can be derived from the mevalonic acid (MVA) and methylerythritol phosphate (MEP) pathways. The absence of two components of the MVA pathway from archaeal genomes led to the discovery of an alternative MVA pathway with isopentenyl phosphate kinase (IPK) catalyzing the final step, the formation of IPP. Despite the fact that plants contain the complete classical MVA pathway, IPK homologs were identified in every sequenced green plant genome. Here, we show that IPK is indeed a member of the plant terpenoid metabolic network. It is localized in the cytosol and is coexpressed with MVA pathway and downstream terpenoid network genes. In planta, IPK acts in parallel with the MVA pathway and plays an important role in regulating the formation of both MVA and MEP pathway-derived terpenoid compounds by controlling the ratio of IP/DMAP to IPP/DMAPP. IP and DMAP can also competitively inhibit farnesyl diphosphate synthase. Moreover, we discovered a metabolically available carbon source for terpenoid formation in plants that is accessible via IPK overexpression. This metabolite reactivation approach offers new strategies for metabolic engineering of terpenoid production.
authors.affiliation: Department of Biochemistry, Purdue University, West Lafayette, IN 47907;
authors.forename: Laura K
authors.initials: LK
authors.lastname: Henry
authors.affiliation: Department of Horticulture and Landscape Architecture, Purdue University, West Lafayette, IN 47907;
authors.forename: Michael
authors.initials: M
authors.lastname: Gutensohn
authors.affiliation: Jack H. Skirball Center for Chemical Biology and Proteomics, Salk Institute for Biological Studies, La Jolla, CA 92037;
authors.forename: Suzanne T
authors.initials: ST
authors.lastname: Thomas
authors.affiliation: Jack H. Skirball Center for Chemical Biology and Proteomics, Salk Institute for Biological Studies, La Jolla, CA 92037; Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, CA 92037.
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Noel
authors.affiliation: Department of Biochemistry, Purdue University, West Lafayette, IN 47907; Department of Horticulture and Landscape Architecture, Purdue University, West Lafayette, IN 47907; dudareva@purdue.edu.
authors.forename: Natalia
authors.initials: N
authors.lastname: Dudareva
mesh_terms: D017360:Arabidopsis / Q000201:enzymology* / Q000235:genetics; D029681:Arabidopsis Proteins / Q000235:genetics / Q000378:metabolism*; D001105:Archaea / Q000201:enzymology*; D003600:Cytosol / Q000378:metabolism; D018506:Gene Expression Regulation, Plant; D055786:Gene Knockout Techniques; D017343:Genes, Plant; D045782:Hemiterpenes / Q000378:metabolism; D007700:Kinetics; D053858:Metabolic Networks and Pathways / Q000235:genetics; D008798:Mevalonic Acid / Q000378:metabolism; D009943:Organophosphorus Compounds / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D030821:Plants, Genetically Modified; D018087:Plastids / Q000378:metabolism; D011106:Polyisoprenyl Phosphates / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D012717:Sesquiterpenes / Q000378:metabolism; D013729:Terpenes / Q000378:metabolism*; D014026:Nicotiana / Q000235:genetics
chemical_list: D029681:Arabidopsis Proteins; D045782:Hemiterpenes; D009943:Organophosphorus Compounds; D011106:Polyisoprenyl Phosphates; D012717:Sesquiterpenes; D013729:Terpenes; C004809:isopentenyl pyrophosphate; C043060:3,3-dimethylallyl pyrophosphate; C015234:geranyl pyrophosphate; C004808:farnesyl pyrophosphate; D017853:Phosphotransferases (Alcohol Group Acceptor); C508906:inositol 1,3,4,5,6-pentakisphosphate 2-kinase, Arabidopsis; D008798:Mevalonic Acid
keywords: MEP pathway; MVA pathway; isopentenyl diphosphate; isopentenyl phosphate kinase; plant terpenoids