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.
| Author of HS Reutlingen | Frey, 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 |
| Place of publication: | Weinheim |
| Document Type: | Journal article |
| Language: | English |
| Publication year: | 2021 |
| Volume: | 60 |
| Issue: | 43 |
| Page Number: | 5 |
| First Page: | 23212 |
| Last Page: | 23216 |
| DDC classes: | 540 Chemie |
| Open access?: | Ja |
| Licence (German): |  Creative Commons - CC BY-NC-ND - Namensnennung - Nicht kommerziell - Keine Bearbeitungen 4.0 International |
