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Biotechnology and Bioengineering (BB) | Enzyme, Protein Engineering, and Metabolic Engineering
Development of Non-Immunosuppressive FK506 Derivatives as Antifungal and Neurotrophic Agents
Department of Chemistry and Nanoscience, Ewha Womans University, Seoul 03760, Republic of Korea
Received: November 6, 2019; Accepted: November 12, 2019
J. Microbiol. Biotechnol. 2020; 30(1): 1-10
Published January 28, 2020
Copyright © The Korean Society for Microbiology and Biotechnology.
FK506, also known as tacrolimus, is a clinically important immunosuppressant drug and has promising therapeutic potentials owing to its antifungal, neuroprotective, and neuroregenerative activities. To generate various FK506 derivatives, the structure of FK506 has been modified by chemical methods or biosynthetic pathway engineering. Herein, we describe the mode of the antifungal action of FK506 and the structure–activity relationship of FK506 derivatives in the context of immunosuppressive and antifungal activities. In addition, we discuss the neurotrophic mechanism of FK506 known to date, along with the neurotrophic FK506 derivatives with significantly reduced immunosuppressive activity. This review suggests the possibility to generate novel FK506 derivatives as antifungal as well as neuroregenerative/neuroprotective agents.
FK506, biosynthesis, antifungal activity, neurotrophic activity