Progress and challenges in the biofoundry of immunosuppressants: From process to practice

Biotechnol Bioeng. 2022 Dec;119(12):3339-3369. doi: 10.1002/bit.28231. Epub 2022 Oct 8.

Abstract

Microorganisms are known to produce pharmaceutically important secondary metabolites that are used as drug moieties in the treatment of various disorders. Discovery of one such class of drugs called immunosuppressants led the way for new and improved treatment regimens for the cases of organ rejections as well as for autoimmune diseases. Uncovering the role of these secondary metabolites as immunomodulators had increased their demand in the global drug market. However, this was soon overshadowed by the low amount of product obtained after fermentation and tedious downstream processing for the recovery of product. Hence, continuous efforts are being made to enhance their production by unveiling the basic biosynthetic pathways involved in their synthesis. From unearthing these immunosuppressants to their rapid development towards commercialization, these drugs have gained a significant place in the world market. Hence, the present review is focused on the progress and challenges in the production and downstream processing of different immunosuppressants (tacrolimus, cyclosporine, rapamycin, and mycophenolic acid). This is the first review report on how the market demand of immunosuppressants could be fulfilled by exploring biofoundry approaches to achieve the goal.

Keywords: cyclosporine; immunosuppressive drugs; mycophenolic acid; rapamycin; tacrolimus.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cyclosporine / therapeutic use
  • Immunosuppressive Agents*
  • Mycophenolic Acid
  • Sirolimus
  • Tacrolimus*

Substances

  • Immunosuppressive Agents
  • Tacrolimus
  • Mycophenolic Acid
  • Cyclosporine
  • Sirolimus