title: Rv0989c encodes a novel (E)-geranyl diphosphate synthase facilitating decaprenyl diphosphate biosynthesis in Mycobacterium tuberculosis.
abstract: Mycobacterium tuberculosis (Mtb) has a highly complex cell wall, which is required for both bacterial survival and infection. Cell wall biosynthesis is dependent on decaprenyl diphosphate as a glyco-carrier, which is hence an essential metabolite in this pathogen. Previous biochemical studies indicated (E)-geranyl diphosphate (GPP) is required for the synthesis of decaprenyl diphosphate. Here we demonstrate that Rv0989c encodes the "missing" GPP synthase, representing the first such enzyme to be characterized from bacteria, and which presumably is involved in decaprenyl diphosphate biosynthesis in Mtb. Our investigation also has revealed previously unrecognized substrate plasticity of the farnesyl diphosphate synthases from Mtb, resolving previous discrepancies between biochemical and genetic studies of cell wall biosynthesis.
authors.affiliation: Department of Biochemistry, Biophysics, and Molecular Biology, Iowa State University, Ames, IA 50011, USA.
authors.forename: Francis M
authors.initials: FM
authors.lastname: Mann
authors.forename: Jill A
authors.initials: JA
authors.lastname: Thomas
authors.forename: Reuben J
authors.initials: RJ
authors.lastname: Peters
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism*; D002473:Cell Wall / Q000378:metabolism; D004122:Dimethylallyltranstransferase / Q000235:genetics* / Q000378:metabolism*; D011756:Diphosphates / Q000737:chemistry / Q000378:metabolism*; D004224:Diterpenes / Q000737:chemistry / Q000378:metabolism*; D005204:Farnesol / Q000737:chemistry / Q000378:metabolism; D005410:Flame Ionization; D008401:Gas Chromatography-Mass Spectrometry; D051228:Geranyltranstransferase / Q000235:genetics / Q000378:metabolism; D045782:Hemiterpenes / Q000737:chemistry / Q000378:metabolism; D007536:Isomerism; D007700:Kinetics; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000201:enzymology*; D009943:Organophosphorus Compounds / Q000737:chemistry / Q000378:metabolism; D011106:Polyisoprenyl Phosphates / Q000737:chemistry / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D016415:Sequence Alignment; D012717:Sesquiterpenes / Q000737:chemistry / Q000378:metabolism; D013379:Substrate Specificity
chemical_list: D001426:Bacterial Proteins; D011756:Diphosphates; D004224:Diterpenes; D045782:Hemiterpenes; D009943:Organophosphorus Compounds; D011106:Polyisoprenyl Phosphates; D011994:Recombinant Proteins; D012717:Sesquiterpenes; C511282:geranyl diphosphate; C043060:3,3-dimethylallyl pyrophosphate; D005204:Farnesol; C004808:farnesyl pyrophosphate; D004122:Dimethylallyltranstransferase; D051228:Geranyltranstransferase