A Polyketide Synthase Component for Oxygen Insertion into Polyketide Backbones.
- Meoded RA Institute of Microbiology, Eigenössische Technische Hochschule (ETH) Zurich, Vladimir-Prelog-Weg 4, 8093, Zurich, Switzerland.
- Ueoka R Institute of Microbiology, Eigenössische Technische Hochschule (ETH) Zurich, Vladimir-Prelog-Weg 4, 8093, Zurich, Switzerland.
- Helfrich EJN Institute of Microbiology, Eigenössische Technische Hochschule (ETH) Zurich, Vladimir-Prelog-Weg 4, 8093, Zurich, Switzerland.
- Jensen K Institute of Microbiology, Eigenössische Technische Hochschule (ETH) Zurich, Vladimir-Prelog-Weg 4, 8093, Zurich, Switzerland.
- Magnus N Institute for Biological Sciences, University of Rostock, Albert-Einstein-Straße 3, 18059, Rostock, Germany.
- Piechulla B Institute for Biological Sciences, University of Rostock, Albert-Einstein-Straße 3, 18059, Rostock, Germany.
- Piel J Institute of Microbiology, Eigenössische Technische Hochschule (ETH) Zurich, Vladimir-Prelog-Weg 4, 8093, Zurich, Switzerland.
- 2018-06-14
Published in:
- Angewandte Chemie (International ed. in English). - 2018
Baeyer-Villiger oxidation
biosynthesis
natural products
polyketide synthases
polyketides
Bacterial Proteins
Biosynthetic Pathways
Oxygen
Oxygenases
Polyketide Synthases
Polyketides
Serratia
Substrate Specificity
English
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.
- Language
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- English
- Open access status
- hybrid
- Identifiers
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- DOI 10.1002/anie.201805363
- PMID 29898240
- Persistent URL
- https://sonar.ch/global/documents/76269
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