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Non-mevalonate pathway

The non-mevalonate pathway—also appearing as the mevalonate-independent pathway and the 2-C-methyl-D-erythritol 4-phosphate/1-deoxy-D-xylulose 5-phosphate (MEP/DOXP) pathway—is an alternative metabolic pathway for the biosynthesis of the isoprenoid precursors isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP).[1][2][3] The currently preferred name for this pathway is the MEP pathway, since MEP is the first committed metabolite on the route to IPP.

Isoprenoid precursor biosynthesis edit

The mevalonate pathway (MVA pathway or HMG-CoA reductase pathway) and the MEP pathway are metabolic pathways for the biosynthesis of isoprenoid precursors: IPP and DMAPP. Whereas plants use both MVA and MEP pathway, most organisms only use one of the pathways for the biosynthesis of isoprenoid precursors. In plant cells IPP/DMAPP biosynthesis via the MEP pathway takes place in plastid organelles, while the biosynthesis via the MVA pathway takes place in the cytoplasm.[4] Most gram-negative bacteria, the photosynthetic cyanobacteria and green algae use only the MEP pathway.[5] Bacteria that use the MEP pathway include important pathogens such Mycobacterium tuberculosis.[6]

IPP and DMAPP serve as precursors for the biosynthesis of isoprenoid (terpenoid) molecules used in processes as diverse as protein prenylation, cell membrane maintenance, the synthesis of hormones, protein anchoring and N-glycosylation in all three domains of life.[citation needed] In photosynthetic organisms MEP-derived precursors are used for the biosynthesis of photosynthetic pigments, such as the carotenoids and the phytol chain of chlorophyll and light harvesting pigments.[5]

Bacteria such as Escherichia coli have been engineered for co-expressing biosynthesis genes of both the MEP and the MVA pathway.[7] Distribution of the metabolic fluxes between the MEP and the MVA pathway can be studied using 13C-glucose isotopomers.[8]

 
Non-mevalonate pathway reactions in the biosynthesis of isoprenoids. Redrawn verbatim from the scheme of Qidwai and coworkers [Fig. 2.].[9] Note, the enzyme abbreviations in this figure are non-standard (cf. Eisenreich et al.[10]), but are presented here and reproduced in the table to allow the two sets of data to be used together.

Reactions edit

The reactions of the MEP pathway are as follows, taken primarily from Eisenreich and co-workers, except where the bold labels are additional local abbreviations to assist in connecting the table to the scheme above:[10][9]

Reactants Enzyme Product
Pyruvate (Pyr) and glyceraldehyde 3-phosphate (G3P) DOXP synthase (Dxs; DXP) 1-Deoxy-D-xylulose 5-phosphate (DOXP; DXP)
 
DOXP (DXP) DXP reductoisomerase (Dxr, IspC; DXR) 2-C-methylerythritol 4-phosphate (MEP)
 
MEP 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase (YgbP, IspD; CMS) 4-diphosphocytidyl-2-C-methylerythritol (CDP-ME)
 
CDP-ME 4-diphosphocytidyl-2-C-methyl-D-erythritol kinase (YchB, IspE; CMK) 4-diphosphocytidyl-2-C-methyl-D-erythritol 2-phosphate (CDP-MEP)
 
CDP-MEP 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase (YgbB, IspF; MCS) 2-C-methyl-D-erythritol 2,4-cyclodiphosphate (MEcPP)
 
MEcPP HMB-PP synthase (GcpE, IspG; HDS) (E)-4-Hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP)
 
HMB-PP HMB-PP reductase (LytB, IspH; HDR) Isopentenyl pyrophosphate (IPP) and Dimethylallyl pyrophosphate (DMAPP)
 

 

Inhibition and other pathway research edit

Dxs the first enzyme of the pathway is feedback inhibited by the products IPP and DMAPP. Dxs is active as a homo-dimer and the precise mechanism of enzyme inhibition has been debated in the field. It has been proposed that IPP/DMAPP are competing the co-factor TPP.[11] A more recent study suggested that IPP/DMAPP trigger monomerisation and subsequent degradation of the enzyme, via interaction with a monomer interaction site that differs from the active site of the enzyme.[12]

DXP reductoisomerase (also known as: DXR, DOXP reductoisomerase, IspC, MEP synthase), is a key enzyme in the MEP pathway. It can be inhibited by the natural product fosmidomycin, which is under study as a starting point to develop a candidate antibacterial or antimalarial drug.[13][14][15]

The intermediate, HMB-PP, is a natural activator of human Vγ9/Vδ2 T cells, the major γδ T cell population in peripheral blood, and cells that "play a crucial role in the immune response to microbial pathogens".[16]

  • IspH inhibitors: non-mevalonate Metabolic pathway that is essential for most bacteria but absent in humans, making it an ideal target for antibiotic development. This pathway, called methyl-D-erythritol phosphate (MEP) or non-mevalonate pathway, is responsible for biosynthesis of isoprenoids—molecules required for cell survival in most pathogenic bacteria and hence will be helpful in most usually antibacterial resistant bacteria.[17]

Metabolic engineering of the MEP/Non-mevalonate pathway edit

The MEP pathway has been extensively studied and engineered Escherichia coli, a commonly used microbial species for laboratory research and application.[18] IPP and DMAPP, the products of the MEP pathway can be used as substrates for the heterologous production of terpenoids with high value for application in the pharmaceutical and chemical industry. Upon expression of heterologous genes from different organisms, production of terpenoids like limonene, bisabolene and isoprene could be achieved in different microbial chassis.[19][20][21][22] Studies overexpressing different biosynthesis genes of the pathway revealed that expression of Dxs and Idi, catalyzing the first step and last step of the MEP pathway could significantly increase the yield of MEP derived terpenoids.[19][22] Dxs as the first enzyme of the pathway represents a bottleneck for the flux of carbon that enters the pathway. Idi which interconverts IPP to DMAPP and vice versa seems to be important for providing the respective substrate that is needed upon introduction of a heterologous carbon sink in engineered strains. A lot of metabolic engineering work on the MEP pathway has been done in cyanobacteria, photo-autotrophic microbes that can assimilate carbon dioxide from the atmosphere into various carbon containing metabolites, including terpenoids.[20][19][21] For biotechnology, cyanobacteria are, thus, an attractive platform for the sustainable production of high-value compounds.

References edit

  1. ^ Rohmer M; Rohmer, Michel (1999). "The discovery of a mevalonate-independent pathway for isoprenoid biosynthesis in bacteria, algae and higher plants". Nat Prod Rep. 16 (5): 565–574. doi:10.1039/a709175c. PMID 10584331.
  2. ^ W. Eisenreich; A. Bacher; D. Arigoni; F. Rohdich (2004). "Review Biosynthesis of isoprenoids via the non-mevalonate pathway". Cellular and Molecular Life Sciences. 61 (12): 1401–1426. doi:10.1007/s00018-004-3381-z. PMID 15197467. S2CID 24558920.
  3. ^ Hunter, WN (2007). "The Non-mevalonate Pathway of Isoprenoid Precursor Biosynthesis". Journal of Biological Chemistry. 282 (30): 21573–21577. doi:10.1074/jbc.R700005200. PMID 17442674.
  4. ^ Lichtenthaler H (1999). "The 1-Deoxy-D-xylulose-5-phosphate pathway of isoprenoid biosynthesis in plants". Annual Review of Plant Physiology and Plant Molecular Biology. 50: 47–65. doi:10.1146/annurev.arplant.50.1.47. PMID 15012203.
  5. ^ a b Vranová, Eva; Coman, Diana; Gruissem, Wilhelm (2013-04-29). "Network Analysis of the MVA and MEP Pathways for Isoprenoid Synthesis". Annual Review of Plant Biology. 64 (1): 665–700. doi:10.1146/annurev-arplant-050312-120116. ISSN 1543-5008.
  6. ^ Wiemer, AJ; Hsiao, CH; Wiemer, DF (2010). "Isoprenoid Metabolism as a Therapeutic Target in Gram-Negative Pathogens". Current Topics in Medicinal Chemistry. 10 (18): 1858–1871. doi:10.2174/156802610793176602. PMID 20615187.
  7. ^ Martin MJ, Pitera DJ, Withers ST, Newman JD, Keasling JD (2003). "Engineering a mevalonate pathway in Escherichia coli for production of terpenoids". Nature Biotechnology. 21 (7): 796–802. doi:10.1038/nbt833. PMID 12778056. S2CID 17214504.
  8. ^ Orsi E, Beekwilder J, Peek S, Eggink G, Kengen SW, Weusthuis RA (2020). "Metabolic flux ratio analysis by parallel 13C labeling of isoprenoid biosynthesis in Rhodobacter sphaeroides". Metabolic Engineering. 57: 228–238. doi:10.1016/j.ymben.2019.12.004. PMID 31843486.
  9. ^ a b Qidwai T, Jamal F, Khan MY, Sharma B (2014). "Exploring Drug Targets in Isoprenoid Biosynthetic Pathway for Plasmodium falciparum". Biochemistry Research International. 2014: 657189. doi:10.1155/2014/657189. PMC 4017727. PMID 24864210.
  10. ^ a b Eisenreich W, Bacher A, Arigoni D, Rohdich F (2004). "Biosynthesis of Isoprenoids Via the Non-mevalonate Pathway". Cell. Mol. Life Sci. 61 (12): 1401–26. doi:10.1007/s00018-004-3381-z. PMID 15197467. S2CID 24558920.
  11. ^ Banerjee, Aparajita; Wu, Yan; Banerjee, Rahul; Li, Yue; Yan, Honggao; Sharkey, Thomas D. (June 2013). "Feedback Inhibition of Deoxy-d-xylulose-5-phosphate Synthase Regulates the Methylerythritol 4-Phosphate Pathway". Journal of Biological Chemistry. 288 (23): 16926–16936. doi:10.1074/jbc.m113.464636. ISSN 0021-9258. PMC 3675625. PMID 23612965.
  12. ^ Di, Xueni; Ortega-Alarcon, David; Kakumanu, Ramu; Iglesias-Fernandez, Javier; Diaz, Lucia; Baidoo, Edward E. K.; Velazquez-Campoy, Adrian; Rodríguez-Concepción, Manuel; Perez-Gil, Jordi (2023-05-08). "MEP pathway products allosterically promote monomerization of deoxy-D-xylulose-5-phosphate synthase to feedback-regulate their supply". Plant Communications. 4 (3): 100512. doi:10.1016/j.xplc.2022.100512. hdl:10261/335525. ISSN 2590-3462.
  13. ^ Hale I, O'Neill PM, Berry NG, Odom A, Sharma R (2012). "The MEP pathway and the Development of Inhibitors as Potential Anti-Infective Agents". Med. Chem. Commun. 3 (4): 418–433. doi:10.1039/C2MD00298A.
  14. ^ Jomaa H, Wiesner J, Sanderbrand S, et al. (1999). "Inhibitors of the Nonmevalonate Pathway of Isoprenoid Biosynthesis as Antimalarial Drugs". Science. 285 (5433): 1573–6. doi:10.1126/science.285.5433.1573. PMID 10477522.
  15. ^ C. Zinglé; L. Kuntz; D. Tritsch; C. Grosdemange-Billiard; M. Rohmer (2010). "Isoprenoid Biosynthesis via the Methylerythritol Phosphate Pathway: Structural Variations around Phosphonate Anchor and Spacer of Fosmidomycin, a Potent Inhibitor of Deoxyxylulose Phosphate Reductoisomerase". J. Org. Chem. 75 (10): 3203–3207. doi:10.1021/jo9024732. PMID 20429517.
  16. ^ Eberl M, Hintz M, Reichenberg A, Kollas AK, Wiesner J, Jomaa H (2003). "Microbial Isoprenoid Biosynthesis and Human γδ T cell Activation". FEBS Lett. 544 (1–3): 4–10. doi:10.1016/S0014-5793(03)00483-6. PMID 12782281. S2CID 9930822.
  17. ^ "Research team reports new class of antibiotics active against a wide range of bacteria". MDLinx. 23 December 2020. Retrieved 23 January 2023.[dead link]
  18. ^ Rodrı́guez-Concepción, Manuel; Boronat, Albert (2002-11-01). "Elucidation of the Methylerythritol Phosphate Pathway for Isoprenoid Biosynthesis in Bacteria and Plastids. A Metabolic Milestone Achieved through Genomics". Plant Physiology. 130 (3): 1079–1089. doi:10.1104/pp.007138. PMC 1540259. Retrieved 2023-10-26.
  19. ^ a b c Englund, Elias; Shabestary, Kiyan; Hudson, Elton P.; Lindberg, Pia (2018-09-01). "Systematic overexpression study to find target enzymes enhancing production of terpenes in Synechocystis PCC 6803, using isoprene as a model compound". Metabolic Engineering. 49: 164–177. doi:10.1016/j.ymben.2018.07.004. ISSN 1096-7176.
  20. ^ a b Gao, Xiang; Gao, Fang; Liu, Deng; Zhang, Hao; Nie, Xiaoqun; Yang, Chen (2016-04-13). "Engineering the methylerythritol phosphate pathway in cyanobacteria for photosynthetic isoprene production from CO2". Energy & Environmental Science. 9 (4): 1400–1411. doi:10.1039/C5EE03102H. ISSN 1754-5706.
  21. ^ a b Rodrigues, João S.; Lindberg, Pia (2021-06-01). "Metabolic engineering of Synechocystis sp. PCC 6803 for improved bisabolene production". Metabolic Engineering Communications. 12: e00159. doi:10.1016/j.mec.2020.e00159. ISSN 2214-0301. PMC 7809396.
  22. ^ a b Du, Fu-Liang; Yu, Hui-Lei; Xu, Jian-He; Li, Chun-Xiu (2014-08-31). "Enhanced limonene production by optimizing the expression of limonene biosynthesis and MEP pathway genes in E. coli". Bioresources and Bioprocessing. 1 (1): 10. doi:10.1186/s40643-014-0010-z. ISSN 2197-4365.

mevalonate, pathway, mevalonate, pathway, also, appearing, mevalonate, independent, pathway, methyl, erythritol, phosphate, deoxy, xylulose, phosphate, doxp, pathway, alternative, metabolic, pathway, biosynthesis, isoprenoid, precursors, isopentenyl, pyrophosp. The non mevalonate pathway also appearing as the mevalonate independent pathway and the 2 C methyl D erythritol 4 phosphate 1 deoxy D xylulose 5 phosphate MEP DOXP pathway is an alternative metabolic pathway for the biosynthesis of the isoprenoid precursors isopentenyl pyrophosphate IPP and dimethylallyl pyrophosphate DMAPP 1 2 3 The currently preferred name for this pathway is the MEP pathway since MEP is the first committed metabolite on the route to IPP Contents 1 Isoprenoid precursor biosynthesis 2 Reactions 3 Inhibition and other pathway research 4 Metabolic engineering of the MEP Non mevalonate pathway 5 ReferencesIsoprenoid precursor biosynthesis editThe mevalonate pathway MVA pathway or HMG CoA reductase pathway and the MEP pathway are metabolic pathways for the biosynthesis of isoprenoid precursors IPP and DMAPP Whereas plants use both MVA and MEP pathway most organisms only use one of the pathways for the biosynthesis of isoprenoid precursors In plant cells IPP DMAPP biosynthesis via the MEP pathway takes place in plastid organelles while the biosynthesis via the MVA pathway takes place in the cytoplasm 4 Most gram negative bacteria the photosynthetic cyanobacteria and green algae use only the MEP pathway 5 Bacteria that use the MEP pathway include important pathogens such Mycobacterium tuberculosis 6 IPP and DMAPP serve as precursors for the biosynthesis of isoprenoid terpenoid molecules used in processes as diverse as protein prenylation cell membrane maintenance the synthesis of hormones protein anchoring and N glycosylation in all three domains of life citation needed In photosynthetic organisms MEP derived precursors are used for the biosynthesis of photosynthetic pigments such as the carotenoids and the phytol chain of chlorophyll and light harvesting pigments 5 Bacteria such as Escherichia coli have been engineered for co expressing biosynthesis genes of both the MEP and the MVA pathway 7 Distribution of the metabolic fluxes between the MEP and the MVA pathway can be studied using 13C glucose isotopomers 8 nbsp Non mevalonate pathway reactions in the biosynthesis of isoprenoids Redrawn verbatim from the scheme of Qidwai and coworkers Fig 2 9 Note the enzyme abbreviations in this figure are non standard cf Eisenreich et al 10 but are presented here and reproduced in the table to allow the two sets of data to be used together Reactions editThe reactions of the MEP pathway are as follows taken primarily from Eisenreich and co workers except where the bold labels are additional local abbreviations to assist in connecting the table to the scheme above 10 9 Reactants Enzyme ProductPyruvate Pyr and glyceraldehyde 3 phosphate G3P DOXP synthase Dxs DXP 1 Deoxy D xylulose 5 phosphate DOXP DXP nbsp DOXP DXP DXP reductoisomerase Dxr IspC DXR 2 C methylerythritol 4 phosphate MEP nbsp MEP 2 C methyl D erythritol 4 phosphate cytidylyltransferase YgbP IspD CMS 4 diphosphocytidyl 2 C methylerythritol CDP ME nbsp CDP ME 4 diphosphocytidyl 2 C methyl D erythritol kinase YchB IspE CMK 4 diphosphocytidyl 2 C methyl D erythritol 2 phosphate CDP MEP nbsp CDP MEP 2 C methyl D erythritol 2 4 cyclodiphosphate synthase YgbB IspF MCS 2 C methyl D erythritol 2 4 cyclodiphosphate MEcPP nbsp MEcPP HMB PP synthase GcpE IspG HDS E 4 Hydroxy 3 methyl but 2 enyl pyrophosphate HMB PP nbsp HMB PP HMB PP reductase LytB IspH HDR Isopentenyl pyrophosphate IPP and Dimethylallyl pyrophosphate DMAPP nbsp nbsp Inhibition and other pathway research editDxs the first enzyme of the pathway is feedback inhibited by the products IPP and DMAPP Dxs is active as a homo dimer and the precise mechanism of enzyme inhibition has been debated in the field It has been proposed that IPP DMAPP are competing the co factor TPP 11 A more recent study suggested that IPP DMAPP trigger monomerisation and subsequent degradation of the enzyme via interaction with a monomer interaction site that differs from the active site of the enzyme 12 DXP reductoisomerase also known as DXR DOXP reductoisomerase IspC MEP synthase is a key enzyme in the MEP pathway It can be inhibited by the natural product fosmidomycin which is under study as a starting point to develop a candidate antibacterial or antimalarial drug 13 14 15 The intermediate HMB PP is a natural activator of human Vg9 Vd2 T cells the major gd T cell population in peripheral blood and cells that play a crucial role in the immune response to microbial pathogens 16 IspH inhibitors non mevalonate Metabolic pathway that is essential for most bacteria but absent in humans making it an ideal target for antibiotic development This pathway called methyl D erythritol phosphate MEP or non mevalonate pathway is responsible for biosynthesis of isoprenoids molecules required for cell survival in most pathogenic bacteria and hence will be helpful in most usually antibacterial resistant bacteria 17 Metabolic engineering of the MEP Non mevalonate pathway editThe MEP pathway has been extensively studied and engineered Escherichia coli a commonly used microbial species for laboratory research and application 18 IPP and DMAPP the products of the MEP pathway can be used as substrates for the heterologous production of terpenoids with high value for application in the pharmaceutical and chemical industry Upon expression of heterologous genes from different organisms production of terpenoids like limonene bisabolene and isoprene could be achieved in different microbial chassis 19 20 21 22 Studies overexpressing different biosynthesis genes of the pathway revealed that expression of Dxs and Idi catalyzing the first step and last step of the MEP pathway could significantly increase the yield of MEP derived terpenoids 19 22 Dxs as the first enzyme of the pathway represents a bottleneck for the flux of carbon that enters the pathway Idi which interconverts IPP to DMAPP and vice versa seems to be important for providing the respective substrate that is needed upon introduction of a heterologous carbon sink in engineered strains A lot of metabolic engineering work on the MEP pathway has been done in cyanobacteria photo autotrophic microbes that can assimilate carbon dioxide from the atmosphere into various carbon containing metabolites including terpenoids 20 19 21 For biotechnology cyanobacteria are thus an attractive platform for the sustainable production of high value compounds References edit Rohmer M Rohmer Michel 1999 The discovery of a mevalonate independent pathway for isoprenoid biosynthesis in bacteria algae and higher plants Nat Prod Rep 16 5 565 574 doi 10 1039 a709175c PMID 10584331 W Eisenreich A Bacher D Arigoni F Rohdich 2004 Review Biosynthesis of isoprenoids via the non mevalonate pathway Cellular and Molecular Life Sciences 61 12 1401 1426 doi 10 1007 s00018 004 3381 z PMID 15197467 S2CID 24558920 Hunter WN 2007 The Non mevalonate Pathway of Isoprenoid Precursor Biosynthesis Journal of Biological Chemistry 282 30 21573 21577 doi 10 1074 jbc R700005200 PMID 17442674 Lichtenthaler H 1999 The 1 Deoxy D xylulose 5 phosphate pathway of isoprenoid biosynthesis in plants Annual Review of Plant Physiology and Plant Molecular Biology 50 47 65 doi 10 1146 annurev arplant 50 1 47 PMID 15012203 a b Vranova Eva Coman Diana Gruissem Wilhelm 2013 04 29 Network Analysis of the MVA and MEP Pathways for Isoprenoid Synthesis Annual Review of Plant Biology 64 1 665 700 doi 10 1146 annurev arplant 050312 120116 ISSN 1543 5008 Wiemer AJ Hsiao CH Wiemer DF 2010 Isoprenoid Metabolism as a Therapeutic Target in Gram Negative Pathogens Current Topics in Medicinal Chemistry 10 18 1858 1871 doi 10 2174 156802610793176602 PMID 20615187 Martin MJ Pitera DJ Withers ST Newman JD Keasling JD 2003 Engineering a mevalonate pathway in Escherichia coli for production of terpenoids Nature Biotechnology 21 7 796 802 doi 10 1038 nbt833 PMID 12778056 S2CID 17214504 Orsi E Beekwilder J Peek S Eggink G Kengen SW Weusthuis RA 2020 Metabolic flux ratio analysis by parallel 13C labeling of isoprenoid biosynthesis in Rhodobacter sphaeroides Metabolic Engineering 57 228 238 doi 10 1016 j ymben 2019 12 004 PMID 31843486 a b Qidwai T Jamal F Khan MY Sharma B 2014 Exploring Drug Targets in Isoprenoid Biosynthetic Pathway for Plasmodium falciparum Biochemistry Research International 2014 657189 doi 10 1155 2014 657189 PMC 4017727 PMID 24864210 a b Eisenreich W Bacher A Arigoni D Rohdich F 2004 Biosynthesis of Isoprenoids Via the Non mevalonate Pathway Cell Mol Life Sci 61 12 1401 26 doi 10 1007 s00018 004 3381 z PMID 15197467 S2CID 24558920 Banerjee Aparajita Wu Yan Banerjee Rahul Li Yue Yan Honggao Sharkey Thomas D June 2013 Feedback Inhibition of Deoxy d xylulose 5 phosphate Synthase Regulates the Methylerythritol 4 Phosphate Pathway Journal of Biological Chemistry 288 23 16926 16936 doi 10 1074 jbc m113 464636 ISSN 0021 9258 PMC 3675625 PMID 23612965 Di Xueni Ortega Alarcon David Kakumanu Ramu Iglesias Fernandez Javier Diaz Lucia Baidoo Edward E K Velazquez Campoy Adrian Rodriguez Concepcion Manuel Perez Gil Jordi 2023 05 08 MEP pathway products allosterically promote monomerization of deoxy D xylulose 5 phosphate synthase to feedback regulate their supply Plant Communications 4 3 100512 doi 10 1016 j xplc 2022 100512 hdl 10261 335525 ISSN 2590 3462 Hale I O Neill PM Berry NG Odom A Sharma R 2012 The MEP pathway and the Development of Inhibitors as Potential Anti Infective Agents Med Chem Commun 3 4 418 433 doi 10 1039 C2MD00298A Jomaa H Wiesner J Sanderbrand S et al 1999 Inhibitors of the Nonmevalonate Pathway of Isoprenoid Biosynthesis as Antimalarial Drugs Science 285 5433 1573 6 doi 10 1126 science 285 5433 1573 PMID 10477522 C Zingle L Kuntz D Tritsch C Grosdemange Billiard M Rohmer 2010 Isoprenoid Biosynthesis via the Methylerythritol Phosphate Pathway Structural Variations around Phosphonate Anchor and Spacer of Fosmidomycin a Potent Inhibitor of Deoxyxylulose Phosphate Reductoisomerase J Org Chem 75 10 3203 3207 doi 10 1021 jo9024732 PMID 20429517 Eberl M Hintz M Reichenberg A Kollas AK Wiesner J Jomaa H 2003 Microbial Isoprenoid Biosynthesis and Human gd T cell Activation FEBS Lett 544 1 3 4 10 doi 10 1016 S0014 5793 03 00483 6 PMID 12782281 S2CID 9930822 Research team reports new class of antibiotics active against a wide range of bacteria MDLinx 23 December 2020 Retrieved 23 January 2023 dead link Rodri guez Concepcion Manuel Boronat Albert 2002 11 01 Elucidation of the Methylerythritol Phosphate Pathway for Isoprenoid Biosynthesis in Bacteria and Plastids A Metabolic Milestone Achieved through Genomics Plant Physiology 130 3 1079 1089 doi 10 1104 pp 007138 PMC 1540259 Retrieved 2023 10 26 a b c Englund Elias Shabestary Kiyan Hudson Elton P Lindberg Pia 2018 09 01 Systematic overexpression study to find target enzymes enhancing production of terpenes in Synechocystis PCC 6803 using isoprene as a model compound Metabolic Engineering 49 164 177 doi 10 1016 j ymben 2018 07 004 ISSN 1096 7176 a b Gao Xiang Gao Fang Liu Deng Zhang Hao Nie Xiaoqun Yang Chen 2016 04 13 Engineering the methylerythritol phosphate pathway in cyanobacteria for photosynthetic isoprene production from CO2 Energy amp Environmental Science 9 4 1400 1411 doi 10 1039 C5EE03102H ISSN 1754 5706 a b Rodrigues Joao S Lindberg Pia 2021 06 01 Metabolic engineering of Synechocystis sp PCC 6803 for improved bisabolene production Metabolic Engineering Communications 12 e00159 doi 10 1016 j mec 2020 e00159 ISSN 2214 0301 PMC 7809396 a b Du Fu Liang Yu Hui Lei Xu Jian He Li Chun Xiu 2014 08 31 Enhanced limonene production by optimizing the expression of limonene biosynthesis and MEP pathway genes in E coli Bioresources and Bioprocessing 1 1 10 doi 10 1186 s40643 014 0010 z ISSN 2197 4365 Retrieved from https en wikipedia org w index php title Non mevalonate pathway amp oldid 1193268441, wikipedia, wiki, book, books, library,

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