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The structure of cyclodecatriene collinolactone, its biosynthesis, and semisynthetic analogues: Effects of monoastral phenotype and protection from intracellular oxidative stress

  • Recently described rhizolutin and collinolactone isolated from Streptomyces Gç 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 rhizolutins 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 Alzheimerprotective 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.

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Metadaten
Author of HS ReutlingenFrey, Kerstin; Kemkemer, Ralf
URN:urn:nbn:de:bsz:rt2-opus4-33439
DOI:https://doi.org/10.1002/anie.202106802
ISSN:1433-7851
eISSN:1521-3773
Publisher:Wiley-VCH GmbH
Place of publication:Weinheim
Document Type:Article
Language:English
Year of Publication:2021
Volume:60
Issue:43
Page Number:5
First Page:23212
Last Page:23216
DDC classes:540 Chemie
Open Access?:Ja
Licence (German):License Logo  Creative Commons - CC BY-NC-ND - Namensnennung - Nicht kommerziell - Keine Bearbeitungen 4.0 International