Mechanistic Investigations of PoyD, a Radical S -Adenosyl- l -methionine Enzyme Catalyzing Iterative and Directional Epimerizations in Polytheonamide A Biosynthesis
| Autor: | Benjamin Lefranc, Alhosna Benjdia, Clémence Balty, Olivier Berteau, Alain Guillot, Aubérie Parent, Jérôme Leprince, Xavier Kubiak |
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| Přispěvatelé: | MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Department of Biomolecular Mechanisms, Max Planck Institute for Medical Research [Heidelberg], Max-Planck-Gesellschaft-Max-Planck-Gesellschaft, Différenciation et communication neuronale et neuroendocrine (DC2N), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), European Project: 617053,EC:FP7:ERC,ERC-2013-CoG,NORACHEM(2014), Lefranc, Benjamin, Novel radical chemistry for complex peptide synthesis and engineering - NORACHEM - - EC:FP7:ERC2014-04-01 - 2019-03-31 - 617053 - VALID |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Stereochemistry [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology [CHIM.THER]Chemical Sciences/Medicinal Chemistry 010402 general chemistry 01 natural sciences Biochemistry Catalysis Article 03 medical and health sciences Residue (chemistry) chemistry.chemical_compound Colloid and Surface Chemistry S-Adenosyl-l-methionine Biosynthesis [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB] [SDV.BBM] Life Sciences [q-bio]/Biochemistry Molecular Biology [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology chemistry.chemical_classification Chemistry General Chemistry In vitro 0104 chemical sciences 030104 developmental biology Enzyme [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology Epimer Radical SAM Cysteine |
| Zdroj: | Journal of the American Chemical Society Journal of the American Chemical Society, American Chemical Society, 2018, 140 (7), pp.2469-2477. ⟨10.1021/jacs.7b08402⟩ Journal of the American Chemical Society, 2018, 140 (7), pp.2469-2477. ⟨10.1021/jacs.7b08402⟩ |
| ISSN: | 0002-7863 1520-5126 |
| Popis: | International audience; Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a growing family of bioactive peptides. Among RiPPs, the bacterial toxin polytheonamide A is characterized by a unique set of post-translational modifications catalyzed by novel radical S-adenosyl-l-methionine (SAM) enzymes. Here we show that the radical SAM enzyme PoyD catalyzes in vitro polytheonamide epimerization in a C-to-N directional manner. By combining mutagenesis experiments with labeling studies and investigating the enzyme substrate promiscuity, we deciphered in detail the mechanism of PoyD. We notably identified a critical cysteine residue as a likely key H atom donor and demonstrated that PoyD belongs to a distinct family of radical SAM peptidyl epimerases. In addition, our study shows that the core peptide directly influences the epimerization pattern allowing for production of peptides with unnatural epimerization patterns. |
| Databáze: | OpenAIRE |
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