TY - JOUR U1 - Zeitschriftenartikel, wissenschaftlich - begutachtet (reviewed) A1 - Kemkemer, Ralf A1 - Schmid, Julian A1 - Frey, Kerstin A1 - Schreiner, Matthias A1 - Guerrero Garzón, Jaime Felipe A1 - Stafforst, Luise A1 - Fricke, Jan-Niklas A1 - Schuppe, Michaela A1 - Schiewe, Hajo A1 - Zeeck, Axel A1 - Weber, Tilmann A1 - Usón, Isabel A1 - Decker, Michael A1 - Grond, Stephanie T1 - The structure of cyclodecatriene collinolactone, its biosynthesis, and semisynthetic analogues: Effects of monoastral phenotype and protection from intracellular oxidative stress JF - Angewandte Chemie : a journal of the Gesellschaft Deutscher Chemiker. International edition N2 - 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. Y1 - 2021 UN - https://nbn-resolving.org/urn:nbn:de:bsz:rt2-opus4-33439 SN - 1433-7851 SS - 1433-7851 U6 - https://doi.org/10.1002/anie.202106802 DO - https://doi.org/10.1002/anie.202106802 VL - 60 IS - 43 SP - 23212 EP - 23216 S1 - 5 PB - Wiley CY - Weinheim ER -