DpgC is a metal- and cofactor-free 3,5-dihydroxyphenylacetyl-CoA 1,2-dioxygenase in the vancomycin biosynthetic pathway

Chemistry & Biology
Claire C TsengChristopher T Walsh

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 O(2) 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 C(2)-methylene hydrogens of DPA-CoA at unequal rates, consistent with enzyme-mediated formation of the substrate-derived C(2)-carbanion as an early intermediate. Incubations with (18)O(2) reveal that DpgC transfers both atoms of an O(2) 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 C(2)-peroxy intermediate, followed by enzyme-directed alpha-peroxylactone formation and collapse by O-O bond cleavage.

References

Nov 1, 1989·European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology·P E Reynolds
Apr 18, 1998·Chemistry & Biology·A M van WageningenP J Solenberg
Jul 4, 1998·Natural Product Reports·B J Rawlings
Dec 18, 1998·The Journal of Biological Chemistry·F H VaillancourtL D Eltis
Jul 12, 2001·Proceedings of the National Academy of Sciences of the United States of America·H T ChiuC Khosla
Dec 26, 2001·Proceedings of the National Academy of Sciences of the United States of America·H ChenC T Walsh
Jun 13, 2002·Proceedings of the National Academy of Sciences of the United States of America·Jeff PootoolalGerard D Wright
Nov 19, 2002·Applied Microbiology and Biotechnology·S Fetzner
Feb 22, 2003·Angewandte Chemie·Brian K Hubbard, Christopher T Walsh
Jan 2, 2004·Microbiology·Margherita SosioStefano Donadio
Jan 28, 2004·Biochemistry·Claire C TsengChristopher T Walsh

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Citations

Feb 17, 2010·Applied Microbiology and Biotechnology·Susanne Fetzner, Roberto A Steiner
Jan 19, 2010·Proceedings of the National Academy of Sciences of the United States of America·Roberto A SteinerSusanne Fetzner
Mar 4, 2005·Proceedings of the National Academy of Sciences of the United States of America·Ellen YehChristopher T Walsh
Jan 7, 2014·Chemistry & Biology·Sven ThierbachSusanne Fetzner
Jun 11, 2016·ACS Chemical Biology·Oleksandr YushchukLiliya Horbal
Jan 8, 2015·Biochemistry·Bert-Jan BaasGerrit J Poelarends
Oct 29, 2015·Chemical Science·Natali V Di RussoAdrian E Roitberg
Jun 20, 2007·Nature Chemical Biology·Susanne Fetzner
Jul 30, 2008·Natural Product Reports·Elizabeth S SattelyChristopher T Walsh
Oct 31, 2008·Chembiochem : a European Journal of Chemical Biology·Silke C WenzelRolf Müller
Jun 18, 2009·Chembiochem : a European Journal of Chemical Biology·Paul F Widboom, Steven D Bruner
Jul 12, 2017·Acta Crystallographica. Section D, Structural Biology·Kunhua LiSteven D Bruner
Sep 9, 2016·Chembiochem : a European Journal of Chemical Biology·Anyarat ThanapipatsiriMervyn J Bibb
Apr 17, 2021·The Journal of Chemical Physics·P OrtegaC Sanz-Sanz

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