The adaptations that alkaliphilic fungi have developed due to their extreme habitat, promote the production of active antibiotic compounds with the potential to control microorganisms, causing infections associated with health care. The discovery of novel peptaibols from marine fungi, fungi habitats from saline and soda soils and other unique locations offer further antibiotic discovery findings from natural sources. Our results, together with previous information regarding the effect on pathogenic fungi and cancer cells, show that lipopeptaibols emericellipsins A-E (EmiA-E) from the alkaliphilic fungus E. alkalina is a promising treatment alternative to licensed antifungal drugs for invasive mycosis therapy for multidrug-resistant aspergillosis and cryptococcosis. EmiA was similar to that of amphotericin B against drug-resistant pathogenic fungi. In a continuation of our investigations into chemodiversity and yield of antimicrobial peptides, we focused in this study on the peptaibol production of the Emericellopsis strains derived from different soda and saline environments.

Thirty-eight alkaliphilic and alkalitolerant Emericellopsis strains (E.alkalina, E. cf. maritima, E. cf. terricola, Emericellopsis sp.) isolated from different saline and soda soils and belonging to marine, terrestrial, and soda soil ecological clades were investigated for EmiA biosynthesis. Our strategy to analyze other Emericellopsis sp. from different soda and saline environments proved to be useful in identifying new compounds. The analysis of the Emericellopsis sp. strains (1KS17-1, 2KS17-1) belonging to marine and terrestrial clades from chloride soils revealed another novel form with a mass of 1032.7 Da\as defined by MALDI-TOF Ms/Ms spectra as the EmiA lacking a hydroxyl (dEmiA). Bioactivity-based assays of this dEmiA form detected activity on Aspergillus niger and Candida albicans fungi with MIC 4 and 2 µg/mL respectively. EmiA displayed strong inhibitory effects on cell proliferation and viability of HCT 116 cells in a dose- and time-dependent manners and induced apoptosis.

This study was supported by the Russian Science Foundation (grant no. 21-75-00062) and the Russian Foundation for Basic Research (project no. 20-04-00992 A).