Differences in Metabolite Profiles and Bioactivities of Intra-Strain Variants of Marine Fungus Penicillium antarcticum KMM 4668

Background. During the cultivation of the marine fungus KMM 4668 on solid agar medium, the morphological instability of the strain was observed. As a result of the selection work, five intra-strain variants, named KMM 4711, KMM 4712, KMM 4713, KMM 4714, and KMM 4715, were obtained. Methods: The main objectives of this work were to compare the parent strain and its intra-strain variants using multi-locus phylogenetic analysis and to study the UPLC MS metabolite profiles and cytotoxic activities of their extracts. Results. A study of the original strain, KMM 4668, and its intra-strain variants using multi-locus phylogenetic analysis showed that they are sequence identical and belong to Penicillium antarcticum. UPLC MS metabolite profiling of fungal extracts revealed 20 compounds, including cladosporin-related polyketides, carotane sesquiterpenoids, andrastine meroterpenoids, and alkaloids. It was shown that the intra-strain variants KMM 4713 and KMM 4714 differed most strongly from the others in the increased production of cladosporin-related compounds, carotanoids, and the alkaloid chrysogin. In addition, the influence of fungal extracts on the viability of four mammalian cell lines was investigated. Conclusions. It has been shown that the intra-strain variants of P. antarcticum KMM 4668 may be promising sources of bioactive secondary metabolites.