Basidiomycetes Ganoderma lucidum, Kuehneromyces mutabilis, Flammulina velutipes, Pleurotus ostreatus and Lentinula edodes as Possible Producers of Sterol Biosynthesis Inhibitors

Background. Cardiovascular and infectious diseases, especially those caused by pathogens resistant to existing drugs, remain the most important problem in modern medicine. The development of fundamentally new effective drugs is possible through the search for natural compounds. The use of new search methods and the involvement of new groups of organisms, including basidiomycetes, can significantly increase the efficiency of screening work and, ultimately, lead to the development of new, more effective drugs.

The aim of the work was to identify sterol biosynthesis inhibitors (SBIs) among the metabolic products of higher fungi — Basidiomycetes.

Materials and Methods. Basidiomycetes were grown using the submerged cultivation method. Ethyl acetate extracts from the culture broth and ethanol extracts from the mycelium of the producers were analyzed. The antibacterial and antifungal activity was assessed using the serial dilution method with determination of the minimum inhibitory concentration, as well as the agar diffusion assay. SBIs were detected utilizing a previously developed test system using the Halobacterium salinarum microbial model.

Results. The study of Ganoderma lucidum, Kuehneromyces mutabilis, Flammulina velutipes, Pleurotus ostreatus, and Lentinula edodes strains revealed the ability of many strains to produce SBIs. The extracts of some L. edodes strains, as well as the extracts obtained from the mycelium of G. lucidum and K. mutabilis, were found to contain inhibitors of the early stages of sterol biosynthesis; their suppressive effect on the H. salinarum culture was removed by the addition of mevalonic acid. The antibiotic complexes of other strains apparently contained inhibitors of later (after the formation of mevalonate) stages of sterol biosynthesis. Some strains have also exhibited antibiotic activity, mainly against Gram-positive bacteria and fungi.

Conclusion. Some of the studied strains demonstrated the ability to form inhibitors of the late stages of sterol biosynthesis. The ability to form inhibitors of early (before mevalonate formation) stages of sterol biosynthesis has been demonstrated in several L. edodes strains, as well as in the P. eryngii strain 10 used as a control. 

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