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.

The eggshell that surrounds insect eggs acts as a barrier, protecting against biotic factors and desiccation. The eggshell is a multi-layered structure which is synthesised by the somatic follicle cells that surround the developing oocyte. Although the temporal order of expression of the protein eggshell components goes someway to explaining how the different layers are built up, but how the precise three-dimensional structure is achieved and how lipid components responsible for desiccation resistance are incorporated are poorly understood. In this paper, we demonstrate that wunen, which encodes a lipid phosphate phosphatase, is necessary for fertility in Drosophila females. Compared to sibling controls, females null for wunen lay fewer eggs which subsequently collapse such that no larvae emerge. We show that this is due to a requirement for wunen in the ovarian follicle cells which is needed to produce an ordered and functional eggshell. Knockdown of a septate junction component also results in collapsed eggs, supporting the idea that similar to its role in embryonic tracheal development, Wunen in follicle cells also promotes septate junction function.

Das kürzlich beschriebene Rhizolutin und Collinolacton, das aus Streptomyces Gö 40/10 isoliert wurde, besitzen dasselbe neuartige Kohlenstoffgerüst. Analysen mittels NMR und Kristallstrukturanalyse belegen die Struktur von Collinolacton und machen eine Korrektur der Stereochemie von Rhizolutin erforderlich. Fütterungsexperimente mit isotopenmarkierten Vorstufen zeigen, dass Collinolacton über eine Typ‐I‐Polyketidsynthase mit anschließender Baeyer‐Villiger‐Oxidation synthetisiert wird. CRISPR‐basierte genetische Arbeiten führten zur Entdeckung des Genclusters und einem optimierten Produktionsstamm. Chemische Semisynthesen lieferten Derivate von Collinolacton, welche die Viabilität von L929‐Zellen reduzieren. Fluoreszenzmikroskopie zeigte, dass diese Derivate während der Zellteilung monopolare Spindeln induzieren. Dem beschriebenen Schutz von Rhizolutin gegen Alzheimer folgend studierten wir die neuroprotektiven Eigenschaften von Collinolacton und dessen Derivaten an Glutamat‐sensitiven Zellen (HT22). Tatsächlich zeigt Collinolacton eine Schutzwirkung gegen intrazellulären oxidativen Stress.