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A Polyketide Synthase Component for Oxygen Insertion into Polyketide Backbones
Enzymatic core components from trans‐acyltransferase polyketide synthases (trans‐AT PKSs) catalyze exceptionally diverse biosynthetic transformations to generate structurally complex bioactive compounds. Here we focus on a group of oxygenases identified in various trans‐AT PKS pathways, including th...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6174933/ https://www.ncbi.nlm.nih.gov/pubmed/29898240 http://dx.doi.org/10.1002/anie.201805363 |
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author | Meoded, Roy A. Ueoka, Reiko Helfrich, Eric J. N. Jensen, Katja Magnus, Nancy Piechulla, Birgit Piel, Jörn |
author_facet | Meoded, Roy A. Ueoka, Reiko Helfrich, Eric J. N. Jensen, Katja Magnus, Nancy Piechulla, Birgit Piel, Jörn |
author_sort | Meoded, Roy A. |
collection | PubMed |
description | Enzymatic core components from trans‐acyltransferase polyketide synthases (trans‐AT PKSs) catalyze exceptionally diverse biosynthetic transformations to generate structurally complex bioactive compounds. Here we focus on a group of oxygenases identified in various trans‐AT PKS pathways, including those for pederin, oocydins, and toblerols. Using the oocydin pathway homologue (OocK) from Serratia plymuthica 4Rx13 and N‐acetylcysteamine (SNAC) thioesters as test surrogates for acyl carrier protein (ACP)‐tethered intermediates, we show that the enzyme inserts oxygen into β‐ketoacyl moieties to yield malonyl ester SNAC products. Based on these data and the identification of a non‐hydrolyzed oocydin congener with retained ester moiety, we propose a unified biosynthetic pathway of oocydins, haterumalides, and biselides. By providing access to internal ester, carboxylate pseudostarter, and terminal hydroxyl functions, oxygen insertion into polyketide backbones greatly expands the biosynthetic scope of PKSs. |
format | Online Article Text |
id | pubmed-6174933 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-61749332018-10-15 A Polyketide Synthase Component for Oxygen Insertion into Polyketide Backbones Meoded, Roy A. Ueoka, Reiko Helfrich, Eric J. N. Jensen, Katja Magnus, Nancy Piechulla, Birgit Piel, Jörn Angew Chem Int Ed Engl Communications Enzymatic core components from trans‐acyltransferase polyketide synthases (trans‐AT PKSs) catalyze exceptionally diverse biosynthetic transformations to generate structurally complex bioactive compounds. Here we focus on a group of oxygenases identified in various trans‐AT PKS pathways, including those for pederin, oocydins, and toblerols. Using the oocydin pathway homologue (OocK) from Serratia plymuthica 4Rx13 and N‐acetylcysteamine (SNAC) thioesters as test surrogates for acyl carrier protein (ACP)‐tethered intermediates, we show that the enzyme inserts oxygen into β‐ketoacyl moieties to yield malonyl ester SNAC products. Based on these data and the identification of a non‐hydrolyzed oocydin congener with retained ester moiety, we propose a unified biosynthetic pathway of oocydins, haterumalides, and biselides. By providing access to internal ester, carboxylate pseudostarter, and terminal hydroxyl functions, oxygen insertion into polyketide backbones greatly expands the biosynthetic scope of PKSs. John Wiley and Sons Inc. 2018-07-31 2018-09-03 /pmc/articles/PMC6174933/ /pubmed/29898240 http://dx.doi.org/10.1002/anie.201805363 Text en © 2018 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Communications Meoded, Roy A. Ueoka, Reiko Helfrich, Eric J. N. Jensen, Katja Magnus, Nancy Piechulla, Birgit Piel, Jörn A Polyketide Synthase Component for Oxygen Insertion into Polyketide Backbones |
title | A Polyketide Synthase Component for Oxygen Insertion into Polyketide Backbones |
title_full | A Polyketide Synthase Component for Oxygen Insertion into Polyketide Backbones |
title_fullStr | A Polyketide Synthase Component for Oxygen Insertion into Polyketide Backbones |
title_full_unstemmed | A Polyketide Synthase Component for Oxygen Insertion into Polyketide Backbones |
title_short | A Polyketide Synthase Component for Oxygen Insertion into Polyketide Backbones |
title_sort | polyketide synthase component for oxygen insertion into polyketide backbones |
topic | Communications |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6174933/ https://www.ncbi.nlm.nih.gov/pubmed/29898240 http://dx.doi.org/10.1002/anie.201805363 |
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