Bioprocess Engineering Aspects of Rapamycin (Sirolimus) Production: A Review on Past Achievements and Recent Perspectives

Abstract
In recent times, immunosuppressants are receiving considerable importance globally for its significant contribution in medical field. Rapamycin (sirolimus) is a potent immunosuppressant which has antifungal, anti-aging, neuroprotective, anti-tumor activities. Rapamycin is produced by many strains of Streptomyces hygroscopicus by submerged fermentation technique. Inadequate amount of the drug synthesized by the species leads to a great challenge to the engineers for further development and industrialization of this important polyketide. Therefore, an in-depth study with respect to bioprocess engineering aspects is required for enhanced production of this important antibiotic. In this review, various bioengineering aspects of industrial production of this metabolite viz., metabolic engineering, optimization, strain improvement strategies and kinetics studies have been discussed.