Dihydroxyphenylglycine

(S)-3,5-Dihydroxyphenylglycine or DHPG is a potent agonist of group I metabotropic glutamate receptors (mGluRs) mGluR1 and mGluR5.

[1] (S)-DHPG has been investigated for therapeutic effects in the treatment of neuronal injury (such as those associated with ischemia or hypoxia), cognitive enhancement, and Alzheimer's disease.

[4] DpgA is a type III polyketide synthase and initiates the synthesis by condensing acetyl-CoA with three molecules of malonyl-CoA.

DpgC oxidizes the aromatic intermediate at the benzylic carbon using oxygen to an alpha-keto compound.

DpgC performs this oxidation in absence of any iron, heme, flavin, or pterin cofactors.

First steps of DHPG involving enzyme DpgA. DpgA condenses acetyl-CoA and malonyl-CoA into a polyketide and then cyclizes the polyketide into a C8 intermediate.
DHPG synthesis involving enzymes DpgB and DpgD. Aromatization of the C8 intermediate through dehydration and then alkene isomerization.
Final steps of the biosynthesis of DHPG. The mechanism of DpgC on the intermediate substrate has been proposed by Chen et al. is included.