@article{KemkemerSchmidFreyetal.2021, author = {Kemkemer, Ralf and Schmid, Julian and Frey, Kerstin and Schreiner, Matthias and Guerrero Garz{\´o}n, Jaime Felipe and Stafforst, Luise and Fricke, Jan-Niklas and Schuppe, Michaela and Schiewe, Hajo and Zeeck, Axel and Weber, Tilmann and Us{\´o}n, Isabel and Decker, Michael and Grond, Stephanie}, title = {The structure of cyclodecatriene collinolactone, its biosynthesis, and semisynthetic analogues: Effects of monoastral phenotype and protection from intracellular oxidative stress}, journal = {Angewandte Chemie : a journal of the Gesellschaft Deutscher Chemiker. International edition}, volume = {60}, number = {43}, issn = {1433-7851}, doi = {10.1002/anie.202106802}, institution = {Life Sciences}, pages = {23212 -- 23216}, year = {2021}, abstract = {Recently described rhizolutin and collinolactone isolated from Streptomyces G{\c{c}} 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.}, language = {en} }