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Discovery of a metabolic alternative to the classical mevalonate pathway

Nikki Dellas1, Suzanne T Thomas, Gerard Manning

  • 1Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, United States.

Elife
|December 12, 2013
PubMed

Insights

Researchers discovered a new alternative mevalonate (MVA) pathway in bacteria, involving the enzymes isopentenyl phosphate kinase (IPK) and mevalonate phosphate decarboxylase (MPD). This finding reveals significant variation in essential isoprenoid metabolism across different life forms.

Area of Science:

  • Biochemistry
  • Metabolic Pathways
  • Microbiology

Background:

  • The mevalonate (MVA) pathway is essential for producing isoprenoids in Eukarya, Archaea, and some Bacteria.
  • Statins are clinically used to modulate the MVA pathway.
  • Two MVA pathway components are frequently absent in archaeal genomes, prompting a search for missing elements.

Purpose of the Study:

  • To identify missing components of the MVA pathway in archaeal genomes.
  • To investigate the presence and function of isopentenyl phosphate kinase (IPK) in Bacteria and Eukarya.
  • To uncover alternative MVA pathways and their key enzymes.

Main Methods:

  • Genomic analysis to identify missing MVA pathway enzymes.
  • Biochemical assays to characterize enzyme activity.
  • Comparative genomics to understand evolutionary distribution of metabolic pathways.

Main Results:

  • Discovery of isopentenyl phosphate kinase (IPK) activity in Bacteria and Eukarya, not just Archaea.
  • Identification of a novel enzyme, mevalonate phosphate decarboxylase (MPD), in Chloroflexi bacteria.
  • Demonstration of a functioning alternative MVA pathway utilizing IPK and MPD.

Conclusions:

  • A functional alternative MVA pathway exists, involving IPK and the newly identified MPD.
  • Isoprenoid metabolism exhibits greater variation than previously understood.
  • These findings have implications for understanding microbial metabolism and evolution.
Keywords:
ArchaeaChloroflexiIsopentenyl diphosphateMevalonate pathwayMevalonate phosphate decarboxylasePlants

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