An overview of rapamycin: from discovery to future perspectives.

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 (4R,5R)-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.

authors

Yoo YJ,Kim H,Park SR,Yoon YJ

doi

10.1007/s10295-016-1834-7

subject

Has Abstract

pub_date

2017-05-01 00:00:00

pages

537-553

issue

4-5

eissn

1367-5435

issn

1476-5535

pii

10.1007/s10295-016-1834-7

journal_volume

44

pub_type

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