An overview of rapamycin: from discovery to future perspectives. (1st May 2017)

• Record Type: Journal Article
• Authors: Yoo, Young Ji; Kim, Hanseong; Park, Sung Ryeol; Yoon, Yeo Joon
• Is Part Of: Journal of industrial microbiology & biotechnology. Volume 44:Number 4/5(2017)
• Page Start: 537
• Page End: 553
• Publication Date: 2017-05-01
• Subjects: Rapamycin -- Biological activity -- Mechanism of action -- Biosynthesis -- Production enhancement; Industrial microbiology -- Periodicals; 660.62
• DOI: 10.1007/s10295-016-1834-7
• Languages: English
• ISSNs: 1367-5435

Abstract

Abstract: Rapamycin is an immunosuppressive metabolite produced from several actinomycete species. Besides its immunosuppressive activity, rapamycin and its analogs have additional therapeutic potentials, including antifungal, antitumor, neuroprotective/neuroregenerative, and lifespan extension activities. The core structure of rapamycin is derived from (4 R, 5 R )-4, 5-dihydrocyclohex-1-ene-carboxylic acid that is extended by polyketide synthase. The resulting linear polyketide chain is cyclized by incorporating pipecolate and further decorated by post-PKS modification enzymes. Herein, we review the discovery and biological activities of rapamycin as well as its mechanism of action, mechanistic target, biosynthesis, and regulation. In addition, we introduce the many efforts directed at enhancing the production of rapamycin and generating diverse analogs and also explore future perspectives in rapamycin research. This review will also emphasize the remarkable pilot studies on the biosynthesis and production improvement of rapamycin by Dr. Demain, one of the world's distinguished scientists in industrial microbiology and biotechnology.