2-C-Methyl-D-erythritol-2,4-cyclopyrophosphate

2-C-Methyl-d-erythritol-2,4-cyclodiphosphate
Skeletal formula of 2-C-methyl-D-erythritol-2,4-cyclodiphosphate
Ball-and-stick model of the 2-C-methyl-D-erythritol-2,4-cyclodiphosphate molecule
Names
Systematic IUPAC name
(6S,7R)-2,4,7-Trihydroxy-6-(hydroxymethyl)-6-methyl-1,3,5,2λ5,4λ5-trioxadiphosphocane-2,4-dione
Identifiers
3D model (JSmol)
ChEBI
ChemSpider
KEGG
MeSH 2-methyl-butan-1,2,3,4-tetraol-2,4-cyclopyrophosphate
  • InChI=1S/C5H12O9P2/c1-5(3-6)4(7)2-12-15(8,9)14-16(10,11)13-5/h4,6-7H,2-3H2,1H3,(H,8,9)(H,10,11)/t4-,5+/m1/s1
    Key: SFRQRNJMIIUYDI-UHNVWZDZSA-N
  • CC1(C(COP(=O)(OP(=O)(O1)O)O)O)CO
Properties
C5H12O9P2
Molar mass 278.09 g/mol
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

2-C-Methyl-d-erythritol-2,4-cyclopyrophosphate (MEcPP) (also 2-C-Methyl-d-erythritol-2,4-cyclodiphosphate) is an intermediate in the MEP pathway (non-mevalonate) of isoprenoid precursor biosynthesis. MEcPP is produced by MEcPP synthase (IspF) and is a substrate for HMB-PP synthase (IspG).

Biochemical role

MEcPP is an intermediate in the non-mevalonate pathway for the biosynthesis of the isoprenoid precursors isopentenyl pyrophosphate and dimethylallyl pyrophosphate. Most gram-negative bacteria, the photosynthetic cyanobacteria and green algae use only this pathway, while higher plants also use the mevalonate pathway.

The enzyme 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase, splits 4-diphosphocytidyl-2-C-methyl-D-erythritol 2-phosphate (CDP-MEP) into MEcPP and cytidine monophosphate.

2D representation of the chemical structure of 4-Diphosphocytidyl-2-C-methyl-D-erythritol 2-phosphate.

CDP-MEP

 
 
 
Rightward reaction arrow
 
 
 

2D representation of the chemical structure of Q27103069.

MEcPP

+
 

2D representation of the chemical structure of cytidine monophosphate .

cytidine monophosphate

Next, 4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase uses two reduced ferredoxin proteins per molecule of MEcPP to convert it to (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP):

MEcPP + 2 oxidised ferredoxin
 
 
 
H2O
Rightward reaction arrow with minor product(s) to top right
 
 
 

2D representation of the chemical structure of Q76285996.

HMB-PP

+ 2 reduced ferredoxin
 

Under conditions of oxidative stress, MEcPP accumulates in certain bacteria. MEcPP releases histone-like proteins from DNA, triggering nucleoid decondensation in Chlamydia trachomatis during the process of terminal differentiation. Abiotic stresses to plants, including wounding and excessive high-light exposure, lead to an increase in MEcPP accumulation in chloroplasts. Transported from the chloroplast to the plant cell nucleus, MEcPP engages in retrograde signalling that leads to the specific induction of nuclear-encoded stress-response genes.

References

  1. 1 2 Herz S, Wungsintaweekul J, Schuhr CA, Hecht S, Lüttgen H, Sagner S, Fellermeier M, Eisenreich W, Zenk MH, Bacher A, Rohdich F (2000). "Biosynthesis of terpenoids: YgbB protein converts 4-diphosphocytidyl-2C-methyl-D-erythritol 2-phosphate to 2C-methyl-D-erythritol 2,4-cyclodiphosphate". Proc. Natl. Acad. Sci. USA. 97 (6): 2486–90. Bibcode:2000PNAS...97.2486H. doi:10.1073/pnas.040554697. PMC 15955. PMID 10694574.
  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. PMC 11138651. 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. ↑ 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.
  5. ↑ 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. Bibcode:2013AnRPB..64..665V. doi:10.1146/annurev-arplant-050312-120116. ISSN 1543-5008. PMID 23451776.
  6. ↑ Hecht, Stefan; Eisenreich, Wolfgang; Adam, Petra; Amslinger, Sabine; Kis, Klaus; Bacher, Adelbert; Arigoni, Duilio; Rohdich, Felix (2001). "Studies on the nonmevalonate pathway to terpenes: The role of the GcpE (IspG) protein". Proceedings of the National Academy of Sciences. 98 (26): 14837–14842. doi:10.1073/pnas.201399298. PMC 64945. PMID 11752431.
  7. ↑ Okada, Ken; Hase, Toshiharu (2005). "Cyanobacterial Non-mevalonate Pathway". Journal of Biological Chemistry. 280 (21): 20672–20679. doi:10.1074/jbc.M500865200. PMID 15792953.
  8. ↑ Ostrovsky D, Shashkov A, Sviridov A (1993). "Bacterial oxidative-stress substance is 2-C-methyl-D-erythritol 2,4-cyclopyrophosphate". Biochem J. 295 (3): 901–2. doi:10.1042/bj2950901. PMC 1134649. PMID 8240308.
  9. ↑ Grieshaber NA, Fischer ER, Mead DJ, Dooley CA, Hackstadt T (2004). "Chlamydial histone-DNA interactions are disrupted by a metabolite in the methylerythritol phosphate pathway of isoprenoid biosynthesis". Proc. Natl. Acad. Sci. USA. 101 (19): 7451–6. doi:10.1073/pnas.0400754101. PMC 409939. PMID 15123794.
  10. ↑ Xiao Y, Savchenko T, Baidoo EE, Chehab WE, Hayden DM, Tolstikov V, Corwin JA, Kliebenstein DJ, Keasling JD, Dehesh K (2012). "Retrograde signaling by the plastidial metabolite MEcPP regulates expression of nuclear stress-response genes". Cell. 149 (7): 1525–35. doi:10.1016/j.cell.2012.04.038. PMID 22726439.