Effect of Starch Composition on the Biosynthesis of Immunosuppressant Tacrolimus (FK-506) by Streptomyces tsukubaensis VKM Ac-2618D Strain

Abstract

The dependence of biosynthesis of macrolide immunosuppressive agent tacrolimus (FK-506) in starch-containing media by the Streptomyces tsukubaensis VKM Ac-2618D strain on the molecular weight and composition of potato starch polysaccharides was studied. It was shown that the use of high-molecular branched starches as a carbon source provided a higher tacrolimus yield as compared to linear low-molecular polysaccharides at the similar culture growth indicators. The approaches providing the highest rate of tacrolimus biosynthesis by using high- and low-molecular starches and dextrins have been proposed. The biosynthesis process carrying out under the periodic batch cultivation with fractional starch feeding increased the tacrolimus yield significantly (up to 2 times), maintained biomass at a high level and reduced destructive processes rates. The maximum tacrolimus titer was observed when high-molecular potato starches were added to the culture in the retardation growth phase, while the best positive effect for low-molecular starches and dextrins additives was noted at stationary growth phase. The results could be useful in creating biotechnology for the production of pharmaceutical tacrolimus.