Isopentenyl diphosphate biosynthesis via a mevalonate-independent pathway: Isopentenyl monophosphate kinase catalyzes the terminal enzymatic step

Bm, Lange; Croteau, Rodney

doi:10.1073/pnas.96.24.13714

Cited by 103 publications

(65 citation statements)

References 36 publications

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“…Higher plants contain orthologs of all relevant yeast genes. Genes coding for the enzymes comprising the alternative DXP pathway also are present in higher plants, in agreement with the biochemical evidence of both pathways in green algae and in dicots (Disch et al 1998;Lange et al 1998;Lange and Croteau 1999).…”

Section: Defining the Orthologs: Only Higher Plants Have The Full Comsupporting

confidence: 63%

“…Recently, a role in the DXP pathway has been proposed for another member of this superfamily, called YchB in E. coli (indicated by 12 in Fig. 1), which is capable of forming IPP by phosphorylation of an isopentenyl monophosphate (IMP) precursor, and also phosphorylates the essential intermediate phosphocytidyl-2-C-methylerythritol (Lange and Croteau 1999;Luttgen et al 2000). We found that related sequence motifs are present in diphosphomevalonate decarboxylases.…”

Section: Detailing the Motifs: New Sequence Relationships For Three Ementioning

confidence: 93%

“…Recent discovery of isopentenyl monophosphate kinase in plants and bacteria suggests that the mevalonate pathway and the DXP pathway may converge at the formation of IPP (Lange and Croteau 1999; Fig. 1).…”

Section: Genome Research 1477mentioning

confidence: 99%

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Biosynthesis of Isoprenoids via Mevalonate in Archaea: The Lost Pathway

Smit

Mushegian²

2000

Genome Res.

124

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Isoprenoid compounds are ubiquitous in living species and diverse in biological function. Isoprenoid side chains of the membrane lipids are biochemical markers distinguishing archaea from the rest of living forms. The mevalonate pathway of isoprenoid biosynthesis has been defined completely in yeast, while the alternative, deoxy-D-xylulose phosphate synthase pathway is found in many bacteria. In archaea, some enzymes of the mevalonate pathway are found, but the orthologs of three yeast proteins, accounting for the route from phosphomevalonate to geranyl pyrophosphate, are missing, as are the enzymes from the alternative pathway. To understand the evolution of isoprenoid biosynthesis, as well as the mechanism of lipid biosynthesis in archaea, sequence motifs in the known enzymes of the two pathways of isoprenoid biosynthesis were analyzed. New sequence relationships were detected, including similarities between diphosphomevalonate decarboxylase and kinases of the galactokinase superfamily, between the metazoan phosphomevalonate kinase and the nucleoside monophosphate kinase superfamily, and between isopentenyl pyrophosphate isomerases and MutT pyrophosphohydrolases. Based on these findings, orphan members of the galactokinase, nucleoside monophosphate kinase, and pyrophosphohydrolase families in archaeal genomes were evaluated as candidate enzymes for the three missing steps. Alternative methods of finding these missing links were explored, including physical linkage of open reading frames and patterns of ortholog distribution in different species. Combining these approaches resulted in the generation of a short list of 13 candidate genes for the three missing functions in archaea, whose participation in isoprenoid biosynthesis is amenable to biochemical and genetic investigation.

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Section: Defining the Orthologs: Only Higher Plants Have The Full Comsupporting

confidence: 63%

Section: Detailing the Motifs: New Sequence Relationships For Three Ementioning

confidence: 93%

See 1 more Smart Citation

Biosynthesis of Isoprenoids via Mevalonate in Archaea: The Lost Pathway

Smit

Mushegian²

2000

Genome Res.

124

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“…5) throughout the GHMP kinase family of phosphotransferases. Moreover, isopentenyl monophosphate kinase also exhibits this motif (23).…”

Section: An Active Site Serine In Mevalonate Kinasementioning

confidence: 99%

Investigation of Invariant Serine/Threonine Residues in Mevalonate Kinase

Cho

Rios

Kim

et al. 2001

Journal of Biological Chemistry

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Mevalonate kinase serine/threonine residues have been implicated in substrate binding and inherited metabolic disease. Alignment of >20 mevalonate kinase sequences indicates that Ser-145, Ser-146, Ser-201, and Thr-243 are the only invariant residues with alcohol side chains. These residues have been individually mutated to alanine. Structural integrity of the mutants has been demonstrated by binding studies using fluorescent and spin-labeled ATP analogs. Kinetic characterization of the mutants indicates only modest changes in K m(ATP) . K m for mevalonate increases by Ϸ20-fold for S146A, Ϸ40-fold for T243A, and 100-fold for S201A. V max changes for S145A, S201A, and T243A are <3-fold. Thus, the 65-fold activity decrease associated with the inherited human T243I mutation seems attributable to the nonconservative substitution rather than any critical catalytic function. V max for S146A is diminished by 4000-fold. In terms of V/K MVA , this substitution produces a 10 5 -fold effect, suggesting an active site location and catalytic role for Ser-146. The large k cat effect suggests that Ser-146 productively orients ATP during catalysis. K D(Mg-ATP) increases by almost 40-fold for S146A, indicating a specific role for Ser-146 in liganding Mg 2؉ -ATP. Instead of mapping within a proposed C-terminal ATP binding motif, Ser-146 is situated in a centrally located motif, which characterizes the galactokinase/homoserine kinase/ mevalonate kinase/phosphomevalonate kinase protein family. These observations represent the first functional demonstration that this region is part of the active site in these related phosphotransferases.Isoprenoid biosynthesis is accomplished by diverse pathways that use either acetyl-CoA (1) or glyceraldehyde 3-phosphate and pyruvate (2) as starting materials. Mevalonate kinase (E.C. 2.7.1.36) represents a distinctive component of the former pathway, which functions in eukaryotes, archaebacteria, and some eubacteria. In the mevalonate-mediated pathway for isoprenoid production, attention has long been focused on HMGCoA 1 reductase, which catalyzes a highly regulated step. The diversity of species in which mevalonate kinase functions is reflected in the high degree of heterology that is apparent upon comparison of deduced sequences for this enzyme. Only 5% of the amino acids that encode the human enzyme are invariant. Included in this select group are the residues (Lys-13, 2 Glu-193, Asp-204) that our laboratory has implicated previously (6, 7) in various active site functions. Inspection of mevalonate kinase's amino acid sequence does not suggest that substrate ATP binding relies on well established consensus sequences such as Walker A or Walker B motifs. However, two distinct glycine-rich stretches of amino acid sequence have been proposed as potential ATP-binding regions (8, 9), although no direct evidence that tests these hypotheses or discriminates between the two candidate sequences has appeared.For phosphotransferase enzymes, there are numerous examples of serines or threonines that map to the...

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“…STC1 was deemed originally to be a sesquiterpene synthase on the basis of the chemical phenotype of stc1 mutants (Shen et al, 2000) and not on the basis of its in vitro product. The presence of a CTP was considered unusual because sesquiterpenes are synthesized in the cytosol via the mevalonic acid pathway, the plastids being the site of synthesis of monoterpenes and diterpenes via the methyl erythritol phosphate or mevalonic acid-independent pathway (Lange and Croteau, 1999). However, natural and engineered exceptions to this compartmentation do occur.…”

Section: Discussionmentioning

confidence: 99%

Characterization of the Monoterpene Synthase Gene tps26, the Ortholog of a Gene Induced by Insect Herbivory in Maize

Lin

Shen

et al. 2008

Plant Physiology

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Plants damaged by insects can synthesize and release volatile chemicals that attract natural enemies of the herbivore. The maize (Zea mays subsp. mays) terpene synthase gene stc1 is part of that indirect defense response, being induced in seedling blades in response to herbivory by beet army worm. Many genes in maize are duplicated because of a past whole-genome duplication event, and several of these orthologs display different expression patterns. We report here the isolation and characterization of tps26 and confirm by homology and synteny criteria that it is the ortholog of stc1. Prior genetic analysis revealed that the stc1 function is not duplicated, raising the interesting question of how the two orthologs have become differentiated in their expression. tps26 encodes a 633-amino acid protein that is highly conserved with STC1. Like stc1, tps26 is induced by wounding, but in the roots and leaf sheath, instead of the blade, and not in response to beet army worm feeding. tps26 maps near a quantitative trait locus for Southwestern corn borer resistance, making it a plausible candidate gene for that quantitative trait locus. However, while possessing highly polymorphic tps26 alleles, the resistant and susceptible parents of the mapping population do not differ in levels of tps26 expression. Moreover, tps26 is not induced specifically by Southwestern corn borer feeding. Therefore, although they share a wounding response, the stc1 and tps26 maize orthologs differ in their tissue specificity and their induction by insect herbivores. The N termini of STC1 and TPS26 are predicted to encode plastid transit peptides; fusion proteins of green fluorescent protein to either N terminus localized to the plastid, confirming that prediction. The mature proteins, but not the respective complete proteins, were active and synthesized a blend of monoterpenes, indicating that they are monoterpene synthases. A gene closely related to stc1/tps26 is found in the sorghum (Sorghum spp.) genome at a location that is not orthologous with stc1. The possible origin of stc1-like genes is discussed.

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Isopentenyl diphosphate biosynthesis via a mevalonate-independent pathway: Isopentenyl monophosphate kinase catalyzes the terminal enzymatic step

Cited by 103 publications

References 36 publications

Biosynthesis of Isoprenoids via Mevalonate in Archaea: The Lost Pathway

Biosynthesis of Isoprenoids via Mevalonate in Archaea: The Lost Pathway

Investigation of Invariant Serine/Threonine Residues in Mevalonate Kinase

Characterization of the Monoterpene Synthase Gene tps26, the Ortholog of a Gene Induced by Insect Herbivory in Maize

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