The Structure of Cyclodecatriene Collinolactone, its Biosynthesis, and Semisynthetic Analogues: Effects of Monoastral Phenotype and Protection from Intracellular Oxidative Stress.

Autor: Schmid JC; Institute of Organic Chemistry, Biomolecular Chemistry, Eberhard Karls University of Tübingen, Auf der Morgenstelle 18, 72076, Tübingen, Germany., Frey K; Department of Applied Chemistry, Reutlingen University, 72762, Reutlingen, Germany., Scheiner M; Pharmaceutical and Medicinal Chemistry, Institute of Pharmacy and Food Chemistry, Julius Maximilians University of Würzburg, 97074, Würzburg, Germany., Garzón JFG; The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, 2800 Kgs., Lyngby, Denmark., Stafforst L; Institute of Organic Chemistry, Biomolecular Chemistry, Eberhard Karls University of Tübingen, Auf der Morgenstelle 18, 72076, Tübingen, Germany., Fricke JN; Institute of Organic Chemistry, Biomolecular Chemistry, Eberhard Karls University of Tübingen, Auf der Morgenstelle 18, 72076, Tübingen, Germany., Schuppe M; Institute of Organic Chemistry, Biomolecular Chemistry, Eberhard Karls University of Tübingen, Auf der Morgenstelle 18, 72076, Tübingen, Germany., Schiewe H; Charles River Laboratories International, Inc., South San Francisco, CA, 94080, United States., Zeeck A; Institute of Organic and Biomolecular Chemistry, Georg August University of Göttingen, 37077, Göttingen, Germany., Weber T; The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, 2800 Kgs., Lyngby, Denmark., Usón I; ICREA, Institució Catalana de Recerca i Estudis Avançats, 08003, Barcelona, Spain.; Crystallographic Methods, Institute of Molecular Biology of Barcelona (IBMB-CSIC), Barcelona Science Park, Helix Building, 08028, Barcelona, Spain., Kemkemer R; Department of Applied Chemistry, Reutlingen University, 72762, Reutlingen, Germany.; Max-Planck-Institute for Medical Research, Jahnstraße 29, 69120, Heidelberg, Germany., Decker M; Pharmaceutical and Medicinal Chemistry, Institute of Pharmacy and Food Chemistry, Julius Maximilians University of Würzburg, 97074, Würzburg, Germany., Grond S; Institute of Organic Chemistry, Biomolecular Chemistry, Eberhard Karls University of Tübingen, Auf der Morgenstelle 18, 72076, Tübingen, Germany.
Jazyk: angličtina
Zdroj: Angewandte Chemie (International ed. in English) [Angew Chem Int Ed Engl] 2021 Oct 18; Vol. 60 (43), pp. 23212-23216. Date of Electronic Publication: 2021 Sep 21.
DOI: 10.1002/anie.202106802
Abstrakt: Recently described rhizolutin and collinolactone isolated from Streptomyces Gö 40/10 share the same novel carbon scaffold. Analyses by NMR and X-Ray crystallography verify the structure of collinolactone and propose a revision of rhizolutin's stereochemistry. Isotope-labeled precursor feeding shows that collinolactone is biosynthesized via type I polyketide synthase with Baeyer-Villiger oxidation. CRISPR-based genetic strategies led to the identification of the biosynthetic gene cluster and a high-production strain. Chemical semisyntheses yielded collinolactone analogues with inhibitory effects on L929 cell line. Fluorescence microscopy revealed that only particular analogues induce monopolar spindles impairing cell division in mitosis. Inspired by the Alzheimer-protective activity of rhizolutin, we investigated the neuroprotective effects of collinolactone and its analogues on glutamate-sensitive cells (HT22) and indeed, natural collinolactone displays distinct neuroprotection from intracellular oxidative stress.
(© 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)
Databáze: MEDLINE
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