Cargando…
New cofactor supports α,β-unsaturated acid decarboxylation via 1,3-dipolar cycloaddition
The ubiD/ubiX or the homologous fdc/pad genes have been implicated in the non-oxidative reversible decarboxylation of aromatic substrates, and play a pivotal role in bacterial ubiquinone biosynthesis1–3 or microbial biodegradation of aromatic compounds4–6 respectively. Despite biochemical studies on...
Autores principales: | , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2015
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4988494/ https://www.ncbi.nlm.nih.gov/pubmed/26083754 http://dx.doi.org/10.1038/nature14560 |
_version_ | 1782448438949969920 |
---|---|
author | Payne, Karl A.P. White, Mark D. Fisher, Karl Khara, Basile Bailey, Samuel S. Parker, David Rattray, Nicholas J.W. Trivedi, Drupad K. Goodacre, Royston Beveridge, Rebecca Barran, Perdita Rigby, Stephen E.J. Scrutton, Nigel S. Hay, Sam Leys, David |
author_facet | Payne, Karl A.P. White, Mark D. Fisher, Karl Khara, Basile Bailey, Samuel S. Parker, David Rattray, Nicholas J.W. Trivedi, Drupad K. Goodacre, Royston Beveridge, Rebecca Barran, Perdita Rigby, Stephen E.J. Scrutton, Nigel S. Hay, Sam Leys, David |
author_sort | Payne, Karl A.P. |
collection | PubMed |
description | The ubiD/ubiX or the homologous fdc/pad genes have been implicated in the non-oxidative reversible decarboxylation of aromatic substrates, and play a pivotal role in bacterial ubiquinone biosynthesis1–3 or microbial biodegradation of aromatic compounds4–6 respectively. Despite biochemical studies on individual gene products, the composition and co-factor requirement of the enzyme responsible for in vivo decarboxylase activity remained unclear7–9. We show Fdc is solely responsible for (de)carboxylase activity, and that it requires a new type of cofactor: a prenylated flavin synthesised by the associated UbiX/Pad10. Atomic resolution crystal structures reveal two distinct isomers of the oxidized cofactor can be observed: an isoalloxazine N5-iminium adduct and a N5 secondary ketimine species with drastically altered ring structure, both having azomethine ylide character. Substrate binding positions the dipolarophile enoic acid group directly above the azomethine ylide group. The structure of a covalent inhibitor-cofactor adduct suggests 1,3-dipolar cycloaddition chemistry supports reversible decarboxylation in these enzymes. While 1,3-dipolar cycloaddition is commonly used in organic chemistry11–12, we propose this presents the first example of an enzymatic 1,3-dipolar cycloaddition reaction. Our model for Fdc/UbiD catalysis offers new routes in alkene hydrocarbon production or aryl (de)carboxylation. |
format | Online Article Text |
id | pubmed-4988494 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
record_format | MEDLINE/PubMed |
spelling | pubmed-49884942016-08-17 New cofactor supports α,β-unsaturated acid decarboxylation via 1,3-dipolar cycloaddition Payne, Karl A.P. White, Mark D. Fisher, Karl Khara, Basile Bailey, Samuel S. Parker, David Rattray, Nicholas J.W. Trivedi, Drupad K. Goodacre, Royston Beveridge, Rebecca Barran, Perdita Rigby, Stephen E.J. Scrutton, Nigel S. Hay, Sam Leys, David Nature Article The ubiD/ubiX or the homologous fdc/pad genes have been implicated in the non-oxidative reversible decarboxylation of aromatic substrates, and play a pivotal role in bacterial ubiquinone biosynthesis1–3 or microbial biodegradation of aromatic compounds4–6 respectively. Despite biochemical studies on individual gene products, the composition and co-factor requirement of the enzyme responsible for in vivo decarboxylase activity remained unclear7–9. We show Fdc is solely responsible for (de)carboxylase activity, and that it requires a new type of cofactor: a prenylated flavin synthesised by the associated UbiX/Pad10. Atomic resolution crystal structures reveal two distinct isomers of the oxidized cofactor can be observed: an isoalloxazine N5-iminium adduct and a N5 secondary ketimine species with drastically altered ring structure, both having azomethine ylide character. Substrate binding positions the dipolarophile enoic acid group directly above the azomethine ylide group. The structure of a covalent inhibitor-cofactor adduct suggests 1,3-dipolar cycloaddition chemistry supports reversible decarboxylation in these enzymes. While 1,3-dipolar cycloaddition is commonly used in organic chemistry11–12, we propose this presents the first example of an enzymatic 1,3-dipolar cycloaddition reaction. Our model for Fdc/UbiD catalysis offers new routes in alkene hydrocarbon production or aryl (de)carboxylation. 2015-06-17 2015-06-25 /pmc/articles/PMC4988494/ /pubmed/26083754 http://dx.doi.org/10.1038/nature14560 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Payne, Karl A.P. White, Mark D. Fisher, Karl Khara, Basile Bailey, Samuel S. Parker, David Rattray, Nicholas J.W. Trivedi, Drupad K. Goodacre, Royston Beveridge, Rebecca Barran, Perdita Rigby, Stephen E.J. Scrutton, Nigel S. Hay, Sam Leys, David New cofactor supports α,β-unsaturated acid decarboxylation via 1,3-dipolar cycloaddition |
title | New cofactor supports α,β-unsaturated acid decarboxylation via 1,3-dipolar cycloaddition |
title_full | New cofactor supports α,β-unsaturated acid decarboxylation via 1,3-dipolar cycloaddition |
title_fullStr | New cofactor supports α,β-unsaturated acid decarboxylation via 1,3-dipolar cycloaddition |
title_full_unstemmed | New cofactor supports α,β-unsaturated acid decarboxylation via 1,3-dipolar cycloaddition |
title_short | New cofactor supports α,β-unsaturated acid decarboxylation via 1,3-dipolar cycloaddition |
title_sort | new cofactor supports α,β-unsaturated acid decarboxylation via 1,3-dipolar cycloaddition |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4988494/ https://www.ncbi.nlm.nih.gov/pubmed/26083754 http://dx.doi.org/10.1038/nature14560 |
work_keys_str_mv | AT paynekarlap newcofactorsupportsabunsaturatedaciddecarboxylationvia13dipolarcycloaddition AT whitemarkd newcofactorsupportsabunsaturatedaciddecarboxylationvia13dipolarcycloaddition AT fisherkarl newcofactorsupportsabunsaturatedaciddecarboxylationvia13dipolarcycloaddition AT kharabasile newcofactorsupportsabunsaturatedaciddecarboxylationvia13dipolarcycloaddition AT baileysamuels newcofactorsupportsabunsaturatedaciddecarboxylationvia13dipolarcycloaddition AT parkerdavid newcofactorsupportsabunsaturatedaciddecarboxylationvia13dipolarcycloaddition AT rattraynicholasjw newcofactorsupportsabunsaturatedaciddecarboxylationvia13dipolarcycloaddition AT trivedidrupadk newcofactorsupportsabunsaturatedaciddecarboxylationvia13dipolarcycloaddition AT goodacreroyston newcofactorsupportsabunsaturatedaciddecarboxylationvia13dipolarcycloaddition AT beveridgerebecca newcofactorsupportsabunsaturatedaciddecarboxylationvia13dipolarcycloaddition AT barranperdita newcofactorsupportsabunsaturatedaciddecarboxylationvia13dipolarcycloaddition AT rigbystephenej newcofactorsupportsabunsaturatedaciddecarboxylationvia13dipolarcycloaddition AT scruttonnigels newcofactorsupportsabunsaturatedaciddecarboxylationvia13dipolarcycloaddition AT haysam newcofactorsupportsabunsaturatedaciddecarboxylationvia13dipolarcycloaddition AT leysdavid newcofactorsupportsabunsaturatedaciddecarboxylationvia13dipolarcycloaddition |