Absolute Stereochemistry and Cytotoxic Effects of Vismione E from Marine Sponge-Derived Fungus Aspergillus sp. 1901NT-1.2.2.

The metabolic profile of the Aspergillus sp. 1901NT-1.2.2 sponge-associated fungal strain was investigated using the HPLC MS technique, and more than 23 peaks in the HPLC MS chromatogram were detected. Only two minor peaks were identified as endocrocin and terpene derivative MS data from the GNPS database. The main compound was isolated and identified as known anthraquinone derivative vismione E. The absolute stereochemistry of vismione E was established for the first time using ECD and quantum chemical methods. Vismione E showed high cytotoxic activity against human breast cancer MCF-7 cells, with an IC50 of 9.0 µM, in comparison with low toxicity for normal human breast MCF-10A cells, with an IC50 of 65.3 µM. It was found that vismione E inhibits MCF-7 cell proliferation and arrests the cell cycle in the G1 phase. Moreover, the negative influence of vismione E on MCF-7 cell migration was detected. Molecular docking of vismione E suggested the IMPDH2 enzyme as one of the molecular targets for this anthraquinone derivative.

Metabolite profiles of Paragliomastix luzulae (formerly named as Acremonium striatisporum) KMM 4401 and its co-cultures with Penicillium hispanicum KMM 4689.

The marine holothurian-derived fungal strain KMM 4401 has been identified as Paragliomastix luzulae using 28S rDNA, ITS regions and the partial TEF1 gene sequences. The metabolite profile of the fungal culture was studied by UPLC-MS technique. The strain KMM 4401 is a source of various virescenoside-type isopimarane glycosides suggested as chemotaxonomic feature for this fungal species. Also Px. luzulae KMM 4401 was proposed as possible source of new bioactive secondary metabolites especially antimicrobials. Moreover, the co-cultures of Px. luzulae KMM 4401 with another marine fungus Penicillium hispanicum KMM 4689 inoculated simultaneously or after two weeks were investigated by same way. It was shown, that P. hispanicum KMM 4689 suppressed the production of most of Px. luzulae KMM 4401 metabolites. On the other hand, the co-cultivation of P. hispanicum KMM 4689 and Px. luzulae KMM 4401 resulted in increasing of production of main deoxyisoaustamide alkaloids of P. hispanicum KMM 4689 on 50-190%.

The Metabolite Profiling of Aspergillus fumigatus KMM4631 and Its Co-Cultures with Other Marine Fungi.

An Aspergillus fumigatus KMM 4631 strain was previously isolated from a Pacific soft coral Sinularia sp. sample and was found to be a source of a number of bioactive secondary metabolites. The aims of this work are the confirmation of this strain' identification based on ITS, BenA, CaM, and RPB2 regions/gene sequences and the investigation of secondary metabolite profiles of Aspergillus fumigatus KMM 4631 culture and its co-cultures with Penicillium hispanicum KMM 4689, Amphichorda sp. KMM 4639, Penicillium sp. KMM 4672, and Asteromyces cruciatus KMM 4696 from the Collection of Marine Microorganisms (PIBOC FEB RAS, Vladivostok, Russia). Moreover, the DPPH-radical scavenging activity, urease inhibition, and cytotoxicity of joint fungal cultures' extracts on HepG2 cells were tested. The detailed UPLC MS qTOF investigation resulted in the identification and annotation of indolediketopiperazine, quinazoline, and tryptoquivaline-related alkaloids as well as a number of polyketides (totally 20 compounds) in the extract of Aspergillus fumigatus KMM 4631. The metabolite profiles of the co-cultures of A. fumigatus with Penicillium hispanicum, Penicillium sp., and Amphichorda sp. were similar to those of Penicillium hispanicum, Penicillium sp., and Amphichorda sp. monocultures. The metabolite profile of the co-culture of A. fumigatus with Asteromyces cruciatus differed from that of each monoculture and may be more promising for the isolation of new compounds.