Effect of Lower Fungi on Tacrolimus Biosynthesis (FK-506) by the Streptomyces tsukubensis VKM Ac-2618D Strain

Abstract

The effect of inactivated yeast cells, cell components of yeast cells, and inactivated biomass of the lower fungi of various taxonomic positions on the immunosuppressant tacrolimus (FK-506) biosynthesis by Streptomyces tsukubensis VKM Ac-2618D has been studied. The fractions of soluble and insoluble components of yeast cells positively influenced the tacrolimus biosynthesis with its concentrations reaching 447.1±22.4 mg/L and 514.3±25.7 mg/L, respectively. Wherein, the insoluble cell components including cell walls and cytoplasmic membranes had a greater effect. The presence of the baker's yeast whole cells and filamentous fungus Aspergillus ochraceus biomass in the complex nutrient medium stimulated the tacrolimus production by S. tsukubensis VKM Ac-2618D (667.5±33.4 mg/L and 633.5±31.7 mg/L, respectively). The biomass of deuteromycete Curvularia lunata had no effect on the FK-506 biosynthesis (288.4±14.4 mg/L). Conversely, the biomass of fungus Gongronella butleri fully inhibited the growth and tacrolimus production by S. tsukubensis. The increase in the FK-506 production in media containing cells of the lower fungi is mainly related to the polysaccharide composition of their cell walls rather than the ergosterol content. The results extend the knowledge on the S. tsukubensis physiology and could be useful for the development of the tacrolimus biotechnological production. tacrolimus, biosynthesis, Streptomyces tsukubensis, yeasts, fungi, ergosterol The study was supported by the FASIE program UMNIK 16-12 (Project no. 12081GU/2017).