Induced secondary metabolites from the endophytic fungus Aspergillus versicolor through bacterial co-culture and OSMAC approaches

• Published in: Tetrahedron letters 2018-07, Vol.59 (27), p.2647-2652
• Main Authors: Abdelwahab, Miada F., Kurtán, Tibor, Mándi, Attila, Müller, Werner E.G., Fouad, Mostafa A., Kamel, Mohamed S., Liu, Zhen, Ebrahim, Weaam, Daletos, Georgios, Proksch, Peter
• Format: Article
• Language: English
• Subjects: Absolute configuration; Aspergillus versicolor; ECD calculations; Tetralone derivatives
• ISSN: 0040-4039; 1873-3581
• DOI: 10.1016/j.tetlet.2018.05.067

[Display omitted] •OSMAC approach was applied for the fungus Aspergillus versicolor.•Co-culture of this fungus with Bacillus subtilis yielded two new tetralones.•ECD calculations were performed for the new tetralone derivatives. Two new cryptic 3,4-dihydronaphthalen-(2H)-1-one (1-tetralone) derivatives, aspvanicin A (1) and its epimer aspvanicin B (2), as well as several known cryptic metabolites (3–8), were obtained from the ethyl acetate extract of the co-culture of the endophytic fungus Aspergillus versicolor KU258497 with the bacterium Bacillus subtilis 168 trpC2 on solid rice medium. When A. versicolor was cultured axenically in liquid Wickerham medium supplemented with 3.5% DMSO, an additional three known secondary metabolites (9–11) were isolated that were lacking when the fungus was fermented on rice medium. The structures of the new compounds were elucidated using one- and two-dimensional NMR spectroscopy as well as HRESIMS. The relative and absolute configurations of 1 and 2 were determined by the combination of NMR and electronic circular dichroism (ECD) analysis aided by DFT conformational analysis and TDDFT-ECD calculations. The ECD calculations revealed that although the sign of the blue-shifted overlapping n-π∗ ECD transition follows the helicity rule of cyclic aryl ketones, the calculation of low-energy conformers and ECD spectra was necessary to determine the stereochemistry. All metabolites were assessed for their antibacterial and cytotoxic activities; one of the new diastereomers, compound 2, showed moderate cytotoxic activity against the mouse lymphoma cell line L5178Y.