Development of Inhibitors of the 2C-Methyl-d-erythritol 4-Phosphate (MEP) Pathway Enzymes as Potential Anti-Infective Agents

2014 ◽  
Vol 57 (23) ◽  
pp. 9740-9763 ◽  
Author(s):  
Tiziana Masini ◽  
Anna K. H. Hirsch
Keyword(s):  
Mep Pathway

Overexpression of SrUGT85C2 from Stevia reduced growth and yield of transgenic Arabidopsis by influencing plastidial MEP pathway

Gene ◽  
2014 ◽  
Vol 539 (2) ◽  
pp. 250-257 ◽  
Author(s):  
Praveen Guleria ◽  
Shikha Masand ◽  
Sudesh Kumar Yadav
Keyword(s):  
Transgenic Arabidopsis ◽  
Mep Pathway ◽  
Growth And Yield

scholarly journals Stable isotope and chemical inhibition analyses suggested the existence of a non-mevalonate-like pathway in the yeast Yarrowia lipolytica

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sivamoke Dissook ◽  
Tomohisa Kuzuyama ◽  
Yuri Nishimoto ◽  
Shigeru Kitani ◽  
Sastia Putri ◽  
...  
Keyword(s):  
Yarrowia Lipolytica ◽  
Oleaginous Yeast ◽  
Isoprenoid Biosynthesis ◽  
Mep Pathway ◽  
Authentic Standard ◽  
Chemical Inhibition ◽  
Chromatographic Peaks ◽  
Methyl Erythritol Phosphate ◽  
Limiting Condition ◽  
Yeast Yarrowia Lipolytica

AbstractMethyl erythritol phosphate (MEP) is the metabolite found in the MEP pathway for isoprenoid biosynthesis, which is known to be utilized by plants, algae, and bacteria. In this study, an unprecedented observation was found in the oleaginous yeast Yarrowia lipolytica, in which one of the chromatographic peaks was annotated as MEP when cultivated in the nitrogen limiting condition. This finding raised an interesting hypothesis of whether Y. lipolytica utilizes the MEP pathway for isoprenoid biosynthesis or not, because there is no report of yeast harboring the MEP pathway. Three independent approaches were used to investigate the existence of the MEP pathway in Y. lipolytica; the spiking of the authentic standard, the MEP pathway inhibitor, and the 13C labeling incorporation analysis. The study suggested that the mevalonate and MEP pathways co-exist in Y. lipolytica and the nitrogen limiting condition triggers the utilization of the MEP pathway in Y. lipolytica.

scholarly journals The Yield of Essential Oils in Melaleuca alternifolia (Myrtaceae) Is Regulated through Transcript Abundance of Genes in the MEP Pathway

PLoS ONE ◽  
2013 ◽  
Vol 8 (3) ◽  
pp. e60631 ◽  
Author(s):  
Hamish Webb ◽  
Robert Lanfear ◽  
John Hamill ◽  
William J. Foley ◽  
Carsten Külheim
Keyword(s):  
Essential Oils ◽  
Transcript Abundance ◽  
Mep Pathway ◽  
Melaleuca Alternifolia

The Non-Mevalonate Isoprenoid Biosynthesis of Plants as a Test System for New Herbicides and Drugs against Pathogenic Bacteria and the Malaria Parasite

2000 ◽  
Vol 55 (5-6) ◽  
pp. 305-313 ◽  
Author(s):  
Hartmut K. Lichtenthaler ◽  
Johannes Zeidler ◽  
Jörg Schwender ◽  
Christian Müller
Keyword(s):  
Malaria Parasite ◽  
Pathogenic Bacteria ◽  
Higher Plants ◽  
Test System ◽  
Isoprenoid Biosynthesis ◽  
Mep Pathway ◽  
New Drugs ◽  
Security Measures ◽  
Isoprenoid Pathway ◽  
Parasite Plasmodium Falciparum

Higher plants and several photosynthetic algae contain the plastidic 1-deoxy-ᴅ-xylulose 5- phosphate / 2-C-methyl-ᴅ-erythritol 4-phosphate pathway (DOXP/MEP pathway) for isoprenoid biosynthesis. The first four enzymes and their genes are known of this novel pathway. All of the ca. 10 enzymes of this isoprenoid pathway are potential targets for new classes of herbicides. Since the DOXP/MEP pathway also occurs in several pathogenic bacteria, such as Mycobacterium tuberculosis, and in the malaria parasite Plasmodium falciparum, all inhibitors and potential herbicides of the DOXP/MEP pathway in plants are also potential drugs against pathogenic bacteria and the malaria parasite. Plants with their easily to handle DOXP/MEP-pathway are thus very suitable test-systems also for new drugs against pathogenic bacteria and the malaria parasite as no particular security measures are required. In fact, the antibiotic herbicide fosmidomycin specifically inhibited not only the DOXP reductoisomerase in plants, but also that in bacteria and in the parasite P. falciparum, and cures malaria-infected mice. This is the first successful application of a herbicide of the novel isoprenoid pathway as a possible drug against malaria.

scholarly journals Overexpression of key enzymes of the 2-C-methyl-D-erythritol-4-phosphate (MEP) pathway for improving squalene production in Escherichia coli

2017 ◽  
Vol 16 (50) ◽  
pp. 2307-2316
Author(s):  
Liu Haiyuan ◽  
Han Shu ◽  
Xie Liping ◽  
Pan Jie ◽  
Zhang Wei ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Mep Pathway ◽  
Key Enzymes

scholarly journals Transcriptomic profiling reveals MEP pathway contributing to ginsenoside biosynthesis in Panax ginseng

BMC Genomics ◽  
2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Le Xue ◽  
Zilong He ◽  
Xiaochun Bi ◽  
Wei Xu ◽  
Ting Wei ◽  
...  
Keyword(s):  
Panax Ginseng ◽  
Mep Pathway ◽  
Transcriptomic Profiling ◽  
Ginsenoside Biosynthesis

scholarly journals Investigation of the methylerythritol 4-phosphate pathway for microbial terpenoid production through metabolic control analysis

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Daniel Christoph Volke ◽  
Johann Rohwer ◽  
Rainer Fischer ◽  
Stefan Jennewein
Keyword(s):  
Metabolic Engineering ◽  
Metabolic Control ◽  
Quantitative Description ◽  
Normal Growth ◽  
Building Blocks ◽  
Metabolic Control Analysis ◽  
Mep Pathway ◽  
Control Analysis ◽  
Significant Control ◽  
Theoretical Yield

Abstract Background Terpenoids are of high interest as chemical building blocks and pharmaceuticals. In microbes, terpenoids can be synthesized via the methylerythritol phosphate (MEP) or mevalonate (MVA) pathways. Although the MEP pathway has a higher theoretical yield, metabolic engineering has met with little success because the regulation of the pathway is poorly understood. Results We applied metabolic control analysis to the MEP pathway in Escherichia coli expressing a heterologous isoprene synthase gene (ispS). The expression of ispS led to the accumulation of isopentenyl pyrophosphate (IPP)/dimethylallyl pyrophosphate (DMAPP) and severely impaired bacterial growth, but the coexpression of ispS and isopentenyl diphosphate isomerase (idi) restored normal growth and wild-type IPP/DMAPP levels. Targeted proteomics and metabolomics analysis provided a quantitative description of the pathway, which was perturbed by randomizing the ribosome binding site in the gene encoding 1-deoxyxylulose 5-phosphate synthase (Dxs). Dxs has a flux control coefficient of 0.35 (i.e., a 1% increase in Dxs activity resulted in a 0.35% increase in pathway flux) in the isoprene-producing strain and therefore exerted significant control over the flux though the MEP pathway. At higher dxs expression levels, the intracellular concentration of 2-C-methyl-d-erythritol-2,4-cyclopyrophosphate (MEcPP) increased substantially in contrast to the other MEP pathway intermediates, which were linearly dependent on the abundance of Dxs. This indicates that 4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase (IspG), which consumes MEcPP, became saturated and therefore limited the flux towards isoprene. The higher intracellular concentrations of MEcPP led to the efflux of this intermediate into the growth medium. Discussion These findings show the importance of Dxs, Idi and IspG and metabolite export for metabolic engineering of the MEP pathway and will facilitate further approaches for the microbial production of valuable isoprenoids.

Diversity in isoprene unit biosynthesis: The methylerythritol phosphate pathway in bacteria and plastids

2007 ◽  
Vol 79 (4) ◽  
pp. 739-751 ◽  
Author(s):  
Michel Rohmer
Keyword(s):  
Mep Pathway ◽  
Reduction Step ◽  
Methylerythritol Phosphate Pathway ◽  
Isoprene Unit ◽  
Methylerythritol Phosphate ◽  
Selection Of

The long-overlooked methylerythritol phosphate (MEP) pathway represents an alternative to the mevalonate route for the formation of isoprene units. It is found in most bacteria as well as in the plastids of all phototrophic organisms. A selection of significant steps of its discovery and elucidation are presented in this contribution, as well as a complete hypothetical biogenetic scheme for the last reduction step.

Engineering the MEP pathway enhanced ajmalicine biosynthesis

2014 ◽  
pp. n/a-n/a ◽  
Author(s):  
Kai Chang ◽  
Fei Qiu ◽  
Min Chen ◽  
Lingjiang Zeng ◽  
Xiaoqiang Liu ◽  
...  
Keyword(s):  
Mep Pathway
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