The biosynthetic pathway of FK506 and its engineering: from past achievements to future prospects

J Ind Microbiol Biotechnol. 2016 Mar;43(2-3):389-400. doi: 10.1007/s10295-015-1677-7. Epub 2015 Sep 5.

Abstract

FK506, a 23-membered macrolide produced by several Streptomyces species, is an immunosuppressant widely used to prevent the rejection of transplanted organs. In addition, FK506 and its analogs possess numerous promising therapeutic potentials including antifungal, neuroprotective, and neuroregenerative activities. Herein, we introduce the biological activities and mechanisms of action of FK506 and discuss recent progress made in understanding its biosynthetic pathway, improving production, and in the mutasynthesis of diverse analogs. Perspectives highlighting further strain improvement and structural diversification aimed at generating more analogs with improved pharmaceutical properties will be emphasized.

Keywords: Biological activity; Biosynthetic pathway; FK506; FK506 analogs; Genetic engineering; Production improvement.

Publication types

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

MeSH terms

  • Animals
  • Biosynthetic Pathways / genetics*
  • Immunosuppressive Agents / metabolism
  • Immunosuppressive Agents / pharmacology
  • Metabolic Engineering / trends*
  • Streptomyces / classification
  • Streptomyces / genetics
  • Streptomyces / metabolism
  • Tacrolimus / analogs & derivatives
  • Tacrolimus / metabolism*
  • Tacrolimus / pharmacology

Substances

  • Immunosuppressive Agents
  • Tacrolimus