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

  • Genetics and Molecular Biology of Industrial Organisms
  • Published:
Journal of Industrial Microbiology & Biotechnology

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.

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Acknowledgments

We thank Dr. Kris Rathwell for critically reading this manuscript. This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (MISP) (2013R1A2A1A01014230), the Intelligent Synthetic Biology Center of the Global Frontier Project funded by MISP (20110031961), Advanced Production Technology Development Program, and High Value-added Food Technology Development Program, Ministry of Agriculture, Food and Rural Affairs, Republic of Korea.

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    1. Department of Chemistry and Nano Science, Ewha Womans University, Seoul, 120-750, Republic of Korea

      Yeon Hee Ban & Yeo Joon Yoon

    2. Life Sciences Institute, University of Michigan, Ann Arbor, MI, 48109, USA

      Sung Ryeol Park

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    Correspondence to Yeo Joon Yoon.

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    Special Issue: Natural Product Discovery and Development in the Genomic Era. Dedicated to Professor Satoshi Ōmura for his numerous contributions to the field of natural products.

    Yeon Hee Ban and Sung Ryeol Park have contributed equally to this work.

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    Ban, Y.H., Park, S.R. & Yoon, Y.J. The biosynthetic pathway of FK506 and its engineering: from past achievements to future prospects. J Ind Microbiol Biotechnol 43, 389–400 (2016). https://doi.org/10.1007/s10295-015-1677-7

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