Streptomyces tsukubensis VKM Aс-2618D - an Effective Producer of Tacrolimus

The identification of the Streptomyces sp. VKM Ac-2618D strain had been carried out and its morphological and physiological features have been studied in relation to the immunosuppressant tacrolimus production. The phenotypic variability of the strain was analyzed and the dissociant with a high level of tacrolimus production was identified. Based on a comprehensive study of morphological, physiological and chemotaxonomic properties, as well as phylogenetic analysis, the strain was named Streptomyces tsukubensis VKM Ac-2618D. The strain genome contains the full version of the tacrolimus biosynthetic gene cluster. The advantages of fed-batch cultivation mode for tacrolimus biosynthesis were shown. The results obtained expand the understanding of the peculiarities of polyketide biosynthesis and can be used in the development of a tacrolimus production technology. Key words: Streptomyces tsukubensis, tacrolimus, FK-506, dissociant, genome, biosynthesis The research was carried out within the framework of the state assignment АААА-А16-116062110077-6.

Biomimetic sponges improve muscle structure and function following volumetric muscle loss

Skeletal muscle is inept in regenerating after traumatic injuries such as volumetric muscle loss (VML) due to significant loss of basal lamina and the resident satellite cells. Currently, there are no approved therapies for the treatment of muscle tissue following trauma. In this study, biomimetic sponges composed of gelatin, collagen, laminin-111, and FK-506 were used for the treatment of VML in a rodent model. We observed that biomimetic sponge treatment improved muscle structure and function while modulating inflammation and limiting the extent of fibrotic tissue deposition. Specifically, sponge treatment increased the total number of myofibers, type 2B fiber cross-sectional area, myosin: collagen ratio, myofibers with central nuclei, and peak isometric torque compared to untreated VML injured muscles. As an acellular scaffold, biomimetic sponges provide a promising “off-the-shelf” clinical therapy for VML.

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

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).