title: Synthesis of methylerythritol phosphate analogues and their evaluation as alternate substrates for IspDF and IspE from Agrobacterium tumefaciens.
abstract: The methylerythritol phosphate biosynthetic pathway, found in most Bacteria, some parasitic protists, and plant chloroplasts, converts D-glyceraldehyde phosphate and pyruvate to isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP), where it intersects with the mevalonate pathway found in some Bacteria, Archaea, and Eukarya, including the cytosol of plants. D-3-Methylerythritol-4-phosphate (MEP), the first pathway-specific intermediate in the pathway, is converted to IPP and DMAPP by the consecutive action of the IspD-H proteins. We synthesized five D-MEP analogues-D-erythritol-4-phosphate (EP), D-3-methylthrietol-4-phosphate (MTP), D-3-ethylerythritol-4-phosphate (EEP), D-1-amino-3-methylerythritol-4-phosphate (NMEP), and D-3-methylerythritol-4-thiolophosphate (MESP)-and studied their ability to function as alternative substrates for the reactions catalyzed by the IspDF fusion and IspE proteins from Agrobacterium tumefaciens, which covert MEP to the corresponding eight-membered cyclic diphosphate. All of the analogues, except MTP, and their products were substrates for the three consecutive enzymes.
authors.affiliation: Department of Chemistry, University of Utah , Salt Lake City, Utah 84112, United States.
authors.forename: Sergiy G
authors.initials: SG
authors.lastname: Krasutsky
authors.forename: Marek
authors.initials: M
authors.lastname: Urbansky
authors.forename: Chad E
authors.initials: CE
authors.lastname: Davis
authors.forename: Christian
authors.initials: C
authors.lastname: Lherbet
authors.forename: Robert M
authors.initials: RM
authors.lastname: Coates
authors.forename: C Dale
authors.initials: CD
authors.lastname: Poulter
mesh_terms: D016960:Agrobacterium tumefaciens / Q000737:chemistry* / Q000201:enzymology* / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry*; D002384:Catalysis; D057075:Enzyme Assays; D004896:Erythritol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D045782:Hemiterpenes / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009097:Multienzyme Complexes / Q000737:chemistry / Q000378:metabolism*; D009943:Organophosphorus Compounds / Q000138:chemical synthesis* / Q000737:chemistry*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000737:chemistry / Q000378:metabolism*; D013379:Substrate Specificity; D013403:Sugar Phosphates / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: C114232:2-C-methylerythritol 4-phosphate; D001426:Bacterial Proteins; C000598092:D-1-amino-3-methylerythritol-4-phosphate; C000598093:D-3-methylerythritol-4-thiolophosphate; D045782:Hemiterpenes; D009097:Multienzyme Complexes; D009943:Organophosphorus Compounds; D013403:Sugar Phosphates; C004809:isopentenyl pyrophosphate; C043060:3,3-dimethylallyl pyrophosphate; D017853:Phosphotransferases (Alcohol Group Acceptor); D004896:Erythritol