Effect of adsorbing resins on the rapamycin biosynthesis by Streptomyces hygroscopicus VKM Ac-2737D
Abstract
V.V. Dzhavakhiya, E.V. Glagoleva, T.M. Voinova, V.V. Savelyeva, A.I. Ovchinnikov, A.V. Matsyura
Rapamycin, a metabolite of Streptomyces hygroscopicus, has a wide range of therapeutic applications in medicine. However, the possibility of its use is significantly limited, since the existing natural strains of this microorganism have rather low productivity that negatively influences the cost of the substance and the possible volumes of its industrial production. At the same time, the commercial use of overproducing strains is also very problematic, since they secrete a large number of metabolites suppressing both the growth of microbial culture and the biosynthesis of a target product. A possible way to solve the problem includes the addition of adsorbents to a fermentation medium for the binding of excess metabolites. In this study, five different selective adsorbing resins, DIAION™ HP20, DIAION™ HP21, DIAION™ HP 20SS, Chromolite, and LPS-500 were tested to provide optimal conditions for the rapamycin biosynthesis by the earlier developed highly-active S. hygroscopicus strain VKM Ac-2737D. The experiments were performed in a 15-L bioreactor using the optimized fermentation medium developed earlier and supplemented with the tested resins. The highest rapamycin yield (1420±5 mg/L) was obtained using a Chromolite 15AD2 adsorbing resin; this result exceeds the earlier obtained yield by 11.4%. The sorptive capacity of this resin was 92% that may significantly facilitate the processes of rapamycin isolation and purification under industrial conditions. The results of the study may be of certain interest for the further scaling-up of the industrial rapamycin production.
Keywords: rapamycin, Streptomyces hygroscopicus, antibiotics, secondary metabolites, fermentation, bioreactor, adsorbing resins