Induction of cryptic metabolites of the endophytic fungus Trichocladium sp. through OSMAC and co-cultivation

• Published in: RSC advances 2019-08, Vol.9 (47), p.27279-27288
• Main Authors: Tran-Cong, Nam Michael, Mándi, Attila, Kurtán, Tibor, Müller, Werner E G, Kalscheuer, Rainer, Lin, Wenhan, Liu, Zhen, Proksch, Peter
• Format: Article
• Language: English
• Subjects: Chemistry; Cultivation; Fungi; Mathematical analysis; Metabolites; NMR; Nuclear magnetic resonance; Peas; Toxicity; Tryptophan
• ISSN: 2046-2069; 2046-2069
• DOI: 10.1039/c9ra05469c

The endophytic fungus sp. isolated from roots of was cultured on solid rice medium, yielding a new amidepsine derivative (1) and a new reduced spiro azaphilone derivative (3) together with eight known compounds (4-11). Co-cultivation of sp. with resulted in induction of a further new compound (2) and a 10-fold increase of 11 compared to the axenic fungal culture. Moreover, when the fungus was cultivated on peas instead of rice, a new sesquiterpene derivative (13) and two known compounds (12 and 14) were obtained. Addition of 2% tryptophan to rice medium led to the isolation of a new bismacrolactone (15). The structures of the new compounds were elucidated by HRESIMS, 1D and 2D NMR as well as by comparison with the literature. A combination of TDDFT-ECD, TDDFT-SOR, DFT-VCD and DFT-NMR calculations were applied to determine the absolute and relative configurations of 13 and 15. Compounds 7, 11 and 15 exhibited strong cytotoxicity against the L5178Y mouse lymphoma cell line with IC values of 0.3, 0.5 and 0.2 μM, respectively.