Negative Feedbacks by Isoprenoids on a Mevalonate Kinase Expressed in the Corpora Allata of Mosquitoes

PLoS One. 2015 Nov 13;10(11):e0143107. doi: 10.1371/journal.pone.0143107. eCollection 2015.


Background: Juvenile hormones (JH) regulate development and reproductive maturation in insects. JHs are synthesized through the mevalonate pathway (MVAP), an ancient metabolic pathway present in the three domains of life. Mevalonate kinase (MVK) is a key enzyme in the MVAP. MVK catalyzes the synthesis of phosphomevalonate (PM) by transferring the γ-phosphoryl group from ATP to the C5 hydroxyl oxygen of mevalonic acid (MA). Despite the importance of MVKs, these enzymes have been poorly characterized in insects.

Results: We functionally characterized an Aedes aegypti MVK (AaMVK) expressed in the corpora allata (CA) of the mosquito. AaMVK displayed its activity in the presence of metal cofactors. Different nucleotides were used by AaMVK as phosphoryl donors. In the presence of Mg(2+), the enzyme has higher affinity for MA than ATP. The activity of AaMVK was regulated by feedback inhibition from long-chain isoprenoids, such as geranyl diphosphate (GPP) and farnesyl diphosphate (FPP).

Conclusions: AaMVK exhibited efficient inhibition by GPP and FPP (Ki less than 1 μM), and none by isopentenyl pyrophosphate (IPP) and dimethyl allyl pyrophosphate (DPPM). These results suggest that GPP and FPP might act as physiological inhibitors in the synthesis of isoprenoids in the CA of mosquitoes. Changing MVK activity can alter the flux of precursors and therefore regulate juvenile hormone biosynthesis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenosine Triphosphate / chemistry
  • Amino Acid Motifs
  • Amino Acid Sequence
  • Animals
  • Catalysis
  • Cations
  • Corpora Allata / enzymology*
  • Culicidae / enzymology*
  • Diphosphates / chemistry
  • Diterpenes / chemistry
  • Female
  • Gene Expression Regulation, Enzymologic*
  • Hydrogen-Ion Concentration
  • Juvenile Hormones / metabolism
  • Magnesium / chemistry
  • Mevalonic Acid / chemistry
  • Molecular Sequence Data
  • Nucleotides / chemistry
  • Oxygen / chemistry
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism*
  • Polyisoprenyl Phosphates / chemistry
  • Protein Conformation
  • Recombinant Proteins / chemistry
  • Sequence Homology, Amino Acid
  • Sesquiterpenes / chemistry
  • Terpenes / chemistry*
  • Thorax / enzymology


  • Cations
  • Diphosphates
  • Diterpenes
  • Juvenile Hormones
  • Nucleotides
  • Polyisoprenyl Phosphates
  • Recombinant Proteins
  • Sesquiterpenes
  • Terpenes
  • geranyl diphosphate
  • farnesyl pyrophosphate
  • Adenosine Triphosphate
  • Phosphotransferases (Alcohol Group Acceptor)
  • mevalonate kinase
  • Magnesium
  • Mevalonic Acid
  • Oxygen