Evaluation of carbon:nitrogen ratio in semi-defined culture medium to tacrolimus biosynthesis by Streptomyces tsukubaensis and the effect on bacterial growth

Abstract

Tacrolimus is an immunosuppressant produced by several Streptomyces species, widely used in transplantolgy and dermatology. In this report, attempts have been made to enhance tacrolimus productivity by altering the primary carbon source on culture media. In order to better understand the effects of glucose and maltose on tacrolimus biosynthesis, different carbon contents of these sugars were evaluated in the culture media, thus altering the carbon:nitrogen ratio. The highest specific production achieved on this report was 10.46 mg/g at a carbon:nitrogen ratio of 8.7:1.0 and maltose as carbon source. Using glucose as primary carbon source, the highest specific production achieved was 9.06 mg/g at a carbon:nitrogen ratio of 8.5:1.0. The range of carbon:nitrogen ratios evaluated for each sugar presented distinct behaviors. Glucose containing-media exhibited an initial linear downward trend, by the other hand, maltose containing-media exhibited an increasing tendency. Both glucose and maltose presented the highest specific production at 3 % of carbon source on media. Media containing more than 3 % of carbon content exerted carbon catabolite repression.The range of carbon:nitogen ratios evaluated presented an increasing tendency on tacrolimus biosynthesis up to 3 % of glucose or maltose in the media, both carbon sources exerted the phenomenon of carbon catabolite repression with more than 3 % of carbon source on the media.