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Non-Mevalonate Pathway: History
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Contributor: Yu Peng

The non-mevalonate pathway is a sequence of enzyme-catalyzed reactions that forms the five-carbon isoprenoid precursors isopentenyl diphosphate and dimethylallyl diphosphate from pyruvate and glyceraldehyde 3-phosphate. It is also termed the methylerythritol phosphate pathway and occurs in many bacteria and in the plastids of plants and several other eukaryotic lineages [1]. The pathway begins with formation of 1-deoxy-D-xylulose 5-phosphate, followed by reductive rearrangement to 2-C-methyl-D-erythritol 4-phosphate. Subsequent cytidylylation, phosphorylation, cyclization, and reductive transformations generate the terminal diphosphate products [2]. Its final two enzymes contain iron–sulfur clusters and require electron transfer for catalysis [3]. Pathway flux depends on precursor supply, enzyme activity, energy availability, and reducing equivalents [4]. The resulting activated five-carbon units participate in downstream chain elongation and the formation of structurally diverse isoprenoid molecules [1][2].

  • MEP pathway
  • isopentenyl diphosphate
  • dimethylallyl diphosphate
  • isoprenoid precursors

References

  1. Jordi Perez-Gil; James Behrendorff; Andrew Douw; Claudia E. Vickers; The Methylerythritol Phosphate Pathway as an Oxidative Stress Sense and Response System. Nat. Commun. 2024, 15, 1-14, 10.1038/s41467-024-49483-8.
  2. Bagmi Pattanaik; Pia Lindberg; Terpenoids and Their Biosynthesis in Cyanobacteria. Life 2015, 5, 269-293, 10.3390/life5010269.
  3. John P. Richard; Tina L. Amyes; On the Importance of Being Zwitterionic: Enzymatic Catalysis of Decarboxylation and Deprotonation of Cationic Carbon. Bioorganic Chem. 2004, 32, 354-366, 10.1016/j.bioorg.2004.05.002.
  4. A. Banerjee; T. D. Sharkey; Methylerythritol 4-phosphate (MEP) Pathway Metabolic Regulation. Nat. Prod. Rep. 2014, 31, 1043-1055, 10.1039/c3np70124g.
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