The biosynthetic pathway of FK506 and its engineering: from past achievements to future prospects.
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.
Department of Chemistry and Nano Science, Ewha Womans University, Seoul, 120-750, Republic of Korea.
Yeon Hee
YH
Ban
Life Sciences Institute, University of Michigan, Ann Arbor, MI, 48109, USA.
Sung Ryeol
SR
Park
Department of Chemistry and Nano Science, Ewha Womans University, Seoul, 120-750, Republic of Korea. joonyoon@ewha.ac.kr.
Yeo Joon
YJ
Yoon
D000818:Animals; D053898:Biosynthetic Pathways / Q000235:genetics*; D007166:Immunosuppressive Agents / Q000378:metabolism / Q000494:pharmacology; D060847:Metabolic Engineering / Q000639:trends*; D013302:Streptomyces / Q000145:classification / Q000235:genetics / Q000378:metabolism; D016559:Tacrolimus / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology
D007166:Immunosuppressive Agents; D016559:Tacrolimus
Biological activity; Biosynthetic pathway; FK506; FK506 analogs; Genetic engineering; Production improvement