scholarly journals Structure-Based Design and Synthesis of the First Weak Non-Phosphate Inhibitors for IspF, an Enzyme in the Non-Mevalonate Pathway of Isoprenoid Biosynthesis

2007 ◽  
Vol 90 (6) ◽  
pp. 1043-1068 ◽  
Author(s):  
Corinne Baumgartner ◽  
Christian Eberle ◽  
François Diederich ◽  
Susan Lauw ◽  
Felix Rohdich ◽  
...  
Keyword(s):  
Mevalonate Pathway ◽  
Isoprenoid Biosynthesis ◽  
Design And Synthesis ◽  
Phosphate Inhibitors

scholarly journals Synthesis and Characterization of Cytidine Derivatives that Inhibit the Kinase IspE of the Non-Mevalonate Pathway for Isoprenoid Biosynthesis

ChemMedChem ◽  
2008 ◽  
Vol 3 (1) ◽  
pp. 91-101 ◽  
Author(s):  
Christine M. Crane ◽  
Anna K. H. Hirsch ◽  
Magnus S. Alphey ◽  
Tanja Sgraja ◽  
Susan Lauw ◽  
...  
Keyword(s):  
Mevalonate Pathway ◽  
Isoprenoid Biosynthesis ◽  
Synthesis And Characterization

The deoxyxylulose phosphate pathway of isoprenoid biosynthesis. Discovery and function of the ispDEFGH genes and their cognate enzymes

2003 ◽  
Vol 75 (2-3) ◽  
pp. 393-405 ◽  
Author(s):  
F. Rohdich ◽  
Stefan Hecht ◽  
Adelbert Bacher ◽  
Wolfgang Eisenreich
Keyword(s):  
Biosynthetic Pathway ◽  
Mevalonate Pathway ◽  
Isoprenoid Biosynthesis ◽  
Catalytic Action ◽  
Isopentenyl Diphosphate ◽  
Dimethylallyl Diphosphate ◽  
And Function

Isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP) serve as the universal precursors for the biosynthesis of terpenes. Besides the well-known mevalonate pathway, a second biosynthetic pathway conducive to IPP and DMAPP via 1-deoxy-d-xylulose-5-phosphate and 2C-methyl-d-erythritol-4-phosphate has been discovered recently in plants and certain eubacteria. 2C-Methyl-d-erythritol-4-phosphate, the first committed intermediate of the deoxyxylulose phosphate pathway, is converted into 2C-methyl-d-erythritol 2,4-cyclodiphosphate by the catalytic action of three enzymes specified by the ispDEF genes. The cyclic diphosphate is reductively opened by the IspG protein affording 1-hydroxy-2-methyl-2-(E)-butenyl-4-diphosphate. This compound can be converted into IPP as well as DMAPP by the catalytic action of IspH protein. The enzymes of this pathway are potential targets for novel antibacterial, antimalarial, and herbicide agents.

Properties and inhibition of the first two enzymes of the non-mevalonate pathway of isoprenoid biosynthesis

2000 ◽  
Vol 28 (6) ◽  
pp. 792-793 ◽  
Author(s):  
C. Mueller ◽  
J. Schwender ◽  
J. Zeidler ◽  
H. K. Lichtenthaler
Keyword(s):  
Escherichia Coli ◽  
Mevalonate Pathway ◽  
Isoprenoid Biosynthesis ◽  
Mep Pathway ◽  
Ph Optimum ◽  
Antibacterial Drugs ◽  
Chloroplast Stroma

Enzymes of the 1-deoxy-D-xylulose 5-phosphate/2-C-methylerythritol 4-phosphate (DOXP/MEP) pathway are targets for new herbicides and antibacterial drugs. Until now, no inhibitors for the DOXP synthase have been known of. We show that one of the breakdown products of the herbicide clomazone affects the DOXP synthase. One inhibitor of the non-mevalonate pathway, fosmidomycin, blocks the DOXP reductoisomerase (DXR) of plants and bacteria. The I50 values of plants are, however, higher than those found for the DXR of Escherichia coli. The DXR of plants, isolated from barley seedlings, shows a pH optimum of 8.1, which is typical for enzymes active in the chloroplast stroma.

8-Substituted,syn-Configured Adenosine Derivatives as Potential Inhibitors of the Enzyme IspE from the Non-Mevalonate Pathway of Isoprenoid Biosynthesis

2015 ◽  
Vol 2015 (33) ◽  
pp. 7276-7286 ◽  
Author(s):  
Michael Harder ◽  
Elisabeth Schäfer ◽  
Tobias Kümin ◽  
Boris Illarionov ◽  
Adelbert Bacher ◽  
...  
Keyword(s):  
Mevalonate Pathway ◽  
Isoprenoid Biosynthesis ◽  
Adenosine Derivatives ◽  
Potential Inhibitors

scholarly journals Isoprenoid biosynthesis via 1-deoxy-D-xylulose 5-phosphate/2-C-methyl-D-erythritol 4-phosphate (DOXP/MEP) pathway.

2001 ◽  
Vol 48 (3) ◽  
pp. 663-672 ◽  
Author(s):  
M Wanke ◽  
K Skorupinska-Tudek ◽  
E Swiezewska
Keyword(s):  
Mevalonate Pathway ◽  
Higher Plants ◽  
Developmental State ◽  
Isoprenoid Biosynthesis ◽  
Mep Pathway ◽  
The Novel ◽  
Dimethylallyl Diphosphate ◽  
Parasite Plasmodium ◽  
Parasite Plasmodium Falciparum ◽  
Mixed Origin

Higher plants, several algae, bacteria, some strains of Streptomyces and possibly malaria parasite Plasmodium falciparum contain the novel, plastidic DOXP/MEP pathway for isoprenoid biosynthesis. This pathway, alternative with respect to the classical mevalonate pathway, starts with condensation of pyruvate and glyceraldehyde-3-phosphate which yields 1-deoxy-D-xylulose 5-phosphate (DOXP); the latter product can be converted to isopentenyl diphosphate (IPP) and eventually to isoprenoids or thiamine and pyridoxal. Subsequent reactions of this pathway involve transformation of DOXP to 2-C-methyl-D-erythritol 4-phosphate (MEP) which after condensation with CTP forms 4-diphosphocytidyl-2-amethyl-D-erythritol (CDP-ME). Then CDP-ME is phosphorylated to 4-diphosphocytidyl-2-amethyl-D-erythritol 2-phosphate (CDP-ME2P) and to 2-C-methyl-D-erythritol-2,4-cyclodiphosphate (ME-2,4cPP) which is the last known intermediate of the DOXP/MEP pathway. For- mation of IPP and dimethylallyl diphosphate (DMAPP) from ME-2,4cPP still requires clarification. This novel pathway appears to be involved in biosynthesis of carotenoids, phytol (side chain of chlorophylls), isoprene, mono-, di-, tetraterpenes and plastoquinone whereas the mevalonate pathway is responsible for formation of sterols, sesquiterpenes and triterpenes. Several isoprenoids were found to be of mixed origin suggesting that some exchange and/or cooperation exists between these two pathways of different biosynthetic origin. Contradictory results described below could indicate that these two pathways are operating under different physiological conditions of the cell and are dependent on the developmental state of plastids.

Structure and reactivity in the non-mevalonate pathway of isoprenoid biosynthesis

2003 ◽  
Vol 31 (3) ◽  
pp. 537-542 ◽  
Author(s):  
W.N. Hunter ◽  
C.S. Bond ◽  
M. Gabrielsen ◽  
L.E. Kemp
Keyword(s):  
Escherichia Coli ◽  
Secondary Structure ◽  
Drug Targets ◽  
Active Sites ◽  
Quaternary Structure ◽  
Mevalonate Pathway ◽  
Isoprenoid Biosynthesis ◽  
Microbial Pathogens ◽  
Function Structure ◽  
Microbial Agents

The function, structure and mechanism of two Escherichia coli enzymes involved in the non-mevalonate route of isoprenoid biosynthesis, 2C-methyl-d-erythritol 4-phosphate cytidylyltransferase and 2C-methyl-d-erythritol 2,4-cyclodiphosphate synthase, are reviewed. Comparisons of each with enzymes from microbial pathogens highlight important conservation of sequence suggestive of similarities in secondary structure, subunit folds, quaternary structure and active sites. Since both enzymes are validated drug targets, the models provide templates for structure-based design of anti-microbial agents targeting a number of serious human diseases.

HmgR, a key enzyme in the mevalonate pathway for isoprenoid biosynthesis, is essential for growth of Listeria monocytogenes EGDe

Microbiology ◽  
2012 ◽  
Vol 158 (7) ◽  
pp. 1684-1693 ◽  
Author(s):  
Sinead Heuston ◽  
Máire Begley ◽  
Martin S. Davey ◽  
Matthias Eberl ◽  
Pat G. Casey ◽  
...  
Keyword(s):  
Listeria Monocytogenes ◽  
Mevalonate Pathway ◽  
Isoprenoid Biosynthesis ◽  
Key Enzyme
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