EFFECTIVE BIOCATALYSTS FOR THE PRODUCTION OF PHARMACOLOGICALLY ACTIVE COMPOUNDS FROM NATURAL STEROLS

Abstract

Bacterial transformation of plant and animal sterols using thegenus Rhodococcus actinobacteria in order to obtain pharmacologically active compounds was studied. It was found that members of Rhodococcus erythropolis, growing in the presence of n-hexadecane and palmitic acid, efficiently (up to 99%) transform β-sitosterol in high (2-10 g/l) concentrations to pharmacologically active stigmast-4-en-3-one. The biotransformation of 10 g/l β-sitosterol was studied in a bioreactor. The level of stigmast-4-en-3-one formation achieves 40% after 22 days from the start of the experiment. The ability of therhodococci cells immobilized on technical polymeric tissue to biotransformation of β-sitosterol under alkaline phosphate buffer (pH 7) was studied. R. erythropolis IEGM 487 strain, catalyzing under these conditions the most effective (50%) transformation of the starting substrate to stigmast-4-ene-3-one, was selected. The level of the target product formation depends on the number of carrier units with fixed bacteria (1 cm2 tissue fragments). Comparative studies of sterol biotransformation with a saturated carbon skeleton in the presence of n-hexadecane or glucose were conducted. The ability of therhodococci to oxidize 5α-cholestane-3β-ol to 5α-cholestane-3-one was found for the first time. R. erythropolis IEGM 490, IEGM 766, IEGM 1017 and IEGM 1018 strains, exhibiting a high (87-100%) transforming activity towards 5α-cholestane-3β-ol regardless of the source of carbon, were selected.