Chemistry & Biology
Volume 11, Issue 9, September 2004, Pages 1195-1203
Journal home page for Chemistry & Biology

Article
DpgC Is a Metal- and Cofactor-Free 3,5-Dihydroxyphenylacetyl-CoA 1,2-Dioxygenase in the Vancomycin Biosynthetic Pathway

https://doi.org/10.1016/j.chembiol.2004.06.012Get rights and content
Under an Elsevier user license
open archive

Abstract

3,5-Dihydroxyphenylglycine is a crucial amino acid monomer in the nonribosomal glycopeptide antibiotic vancomycin. This nonproteinogenic amino acid is constructed from malonyl-CoA by a set of four enzymes, DpgA–D, in the biosynthetic cluster. DpgC is an unusual metal-free, cofactor-free enzyme that consumes O2 during the conversion of 3,5-dihydroxyphenylacetyl-CoA (DPA-CoA) to the penultimate intermediate 3,5-dihydroxyphenylglyoxylate (DPGx). We show that in anaerobic incubations, DpgC catalyzes the exchange of the C2-methylene hydrogens of DPA-CoA at unequal rates, consistent with enzyme-mediated formation of the substrate-derived C2-carbanion as an early intermediate. Incubations with 18O2 reveal that DpgC transfers both atoms of an O2 molecule to DPGx product. This establishes DpgC as a 1,2-dioxygenase that mediates thioester cleavage by the oxygen transfer process. These results are consistent with a DPA-CoA C2-peroxy intermediate, followed by enzyme-directed α-peroxylactone formation and collapse by O-O bond cleavage.

Cited by (0)

1

Present address: Department of Chemistry, Boston College, Chestnut Hill, Massachusetts 02467.