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
Mar 21, 1978·Biochemistry·O ShimomuraY Haneda
Aug 13, 1991·Biochemistry·L M Abell, J V Schloss
Nov 1, 1989·European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology·P E Reynolds
Feb 1, 1970·Analytical Biochemistry·J Robinson, J M Cooper
Jul 6, 1993·Biochemistry·B Shen, C R Hutchinson
Dec 15, 1995·European Journal of Biochemistry·J BucG Giordano
Sep 15, 1996·European Journal of Biochemistry·I BauerF Lingens
Jul 1, 1997·Journal of Bacteriology·S G KendrewE N Marsh
Oct 23, 1997·Biochemistry·A L TsaiR J Kulmacz
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 2, 1999·Antimicrobial Agents and Chemotherapy·S PelzerW Wohlleben
Jan 4, 2001·Chemistry & Biology·B K HubbardC T Walsh
Jul 12, 2001·Proceedings of the National Academy of Sciences of the United States of America·H T ChiuC Khosla
Aug 10, 2001·The Journal of Biological Chemistry·V PfeiferS Pelzer
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
Apr 29, 2004·Chemistry & Biology·Tsung-Lin LiJonathan B Spencer
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
Sep 28, 2013·BMC Genomics·Monique RoyerStéphane Cociancich
Mar 4, 2005·Proceedings of the National Academy of Sciences of the United States of America·Ellen YehChristopher T Walsh
Dec 15, 2010·Journal of Biotechnology·Yvonne J MastEva Schinko
Aug 6, 2011·Microbiology·Fitria NingsihTakuya Nihira
Jun 27, 2013·Metabolic Engineering·Tao ZhuDelin You
Feb 1, 2015·Analytical Biochemistry·Natali V Di RussoAdrian E Roitberg
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
May 18, 2007·Nature·Paul F WidboomSteven D Bruner
Jun 20, 2007·Nature Chemical Biology·Susanne Fetzner
Apr 17, 2008·Molecular BioSystems·Stefan A SamelLars-Oliver Essen
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
Jun 5, 2013·Angewandte Chemie·Christopher T WalshChaitan Khosla
Sep 9, 2016·Chembiochem : a European Journal of Chemical Biology·Anyarat ThanapipatsiriMervyn J Bibb
Sep 26, 2020·Chemistry : a European Journal·Pablo OrtegaPablo G Jambrina
Apr 17, 2021·The Journal of Chemical Physics·P OrtegaC Sanz-Sanz
Mar 3, 2020·ACS Chemical Biology·Bin TanChangsheng Zhang