When synthesized in bacteria, DHPG requires 5 enzymes, DpgA-D and 4-hydroxyphenylglycine transferase (Pgat), in order to be synthesized.
DpgA is a type III polyketide synthase and initiates the synthesis by condensing acetyl-CoA with three molecules of malonyl-CoA. The tetra-carbonyl compound then cyclizes to form a C8 intermediate.
DpgB/D then dehydrates the intermediate using enolate chemistry to promote the loss of water.
DpgB/D isomerizes the product to aromatize the ring.

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.
Chen et al suggest the following reaction mechanism to explain the reactivity of DpgC. This mechanism is supported by findings reported in Widboom et al in 2007.
Finally, the molecule is transaminated by 4-hydroxyphenylglycine transferase using tyrosine to become DHPG.

4-Hydroxyphenylglycine transferase synthesizes the (S) stereoisomer of DHPG, however, an epimerase switches the stereocenter to the (R) configuration after DHPG is incorporated into the vancomycin non-ribosomal polypeptide.
When synthesized in bacteria, DHPG requires 5 enzymes, DpgA-D and 4-hydroxyphenylglycine transferase (Pgat), in order to be synthesized. DpgA is a type III polyketide synthase and initiates the synthesis by condensing acetyl-CoA with three molecules of malonyl-CoA. The tetra-carbonyl compound then cyclizes to form a C8 intermediate. DpgB/D then dehydrates the intermediate using enolate chemistry to promote the loss of water. DpgB/D isomerizes the product to aromatize the ring.
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. Chen et al suggest the following reaction mechanism to explain the reactivity of DpgC. This mechanism is supported by findings reported in Widboom et al in 2007. Finally, the molecule is transaminated by 4-hydroxyphenylglycine transferase using tyrosine to become DHPG.
4-Hydroxyphenylglycine transferase synthesizes the (S) stereoisomer of DHPG, however, an epimerase switches the stereocenter to the (R) configuration after DHPG is incorporated into the vancomycin non-ribosomal polypeptide.
Dihydroxyphenylglycine