Meoded RA Ueoka R Helfrich EJN Jensen K Magnus N Piechulla B Piel J 2018 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. application/pdf https://sonar.ch/global/documents/76269 eng info:eu-repo/semantics/altIdentifier/doi/10.1002/anie.201805363 info:eu-repo/semantics/altIdentifier/pmid/29898240 info:eu-repo/semantics/openAccess 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 A Polyketide Synthase Component for Oxygen Insertion into Polyketide Backbones. http://purl.org/coar/resource_type/c_6501