Journal
JOURNAL OF ANTIBIOTICS
Volume 63, Issue 8, Pages 434-441Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ja.2010.71
Keywords
biological activity; biosynthesis; rapamycin; regulation
Funding
- Korean Government [20090083305, 20090083153, 20100001487]
- Seoul RBD Program [KU080657M0209721]
- Technology Development Program for Fisheries, Ministry for Food, Agriculture, Forestry and Fisheries, Republic of Korea
- National Research Foundation of Korea [2007-03530, 2008-0059999, 2008-0057903] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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Rapamycin and its analogs are clinically important macrolide compounds produced by Streptomyces hygroscopicus. They exhibit antifungal, immunosuppressive, antitumor, neuroprotective and antiaging activities. The core macrolactone ring of rapamycin is biosynthesized by hybrid type I modular polyketide synthase (PKS)/nonribosomal peptide synthetase systems primed with 4,5-dihydrocyclohex-1-ene-carboxylic acid. The linear polyketide chain is condensed with pipecolate by peptide synthetase, followed by cyclization to form the macrolide ring and modified by a series of post-PKS tailoring steps. The aim of this review was to outline past and recent advances in the biosynthesis and regulation of rapamycin, with an emphasis on the distinguished contributions of Professor Demain to the study of rapamycin. In addition, this article describes the biological activities as well as mechanism of action of rapamycin and its derivatives. Recent attempts to improve the productivity of rapamycin and generate diverse rapamycin analogs through mutasynthesis and mutagenesis are also introduced, along with some future perspectives. The Journal of Antibiotics (2010) 63, 434-441, doi 10 1038/ja 2010.71, published online 30 June 2010
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