Reference : The biosynthetic cluster for the polyketide immunosuppressant rapamycin
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/10993/12403
The biosynthetic cluster for the polyketide immunosuppressant rapamycin
English
Schwecke, T. [University of Cambridge > Department of Biochemistry]
Aparicio, J. F. [University of Cambridge > Department of Biochemistry]
Molnár, I. [University of Cambridge > Department of Biochemistry]
König, Ariane mailto [University of Cambridge > Department of Biochemistry > Cambridge Center for Molecular Recognition]
Khaw, L. E. [University of Cambridge > Department of Biochemistry]
Haydock, S. F. [University of Cambridge > Department of Biochemistry]
Olinyk, M. [University of Cambridge > Department of Biochemistry]
Caffrey, P. [University of Cambridge > Department of Biochemistry]
Cortés, J. B. [University of Cambridge > Department of Biochemistry]
Lester, J. [University of Cambridge > Department of Biochemistry]
Böhm, G. A. [University of Cambridge > Department of Biochemistry]
Staunton, J. [University of Cambridge > University Chemical Laboratory]
Leadlay, P. F. [University of Cambridge > Department of Biochemistry]
Aug-1995
Proceedings of the National Academy of Sciences of the United States of America
National Academy of Sciences
92
17
7839-7843
Yes (verified by ORBilu)
International
0027-8424
1091-6490
Washington
DC
[en] FK506 ; peptide synthetase ; polyketide synthase ; Streptomyces
[en] The macrocyclic polyketides rapamycin and FK506 are potent immunosuppressants that prevent T-cell proliferation through specific binding to intracellular protein receptors (immunophilins). The cloning and specific alteration of the biosynthetic genes for these polyketides might allow the biosynthesis of clinically valuable analogues. We report here that three clustered polyketide synthase genes responsible for rapamycin biosynthesis in Streptomyces hygroscopicus together encode 14 homologous sets of enzyme activities (modules), each catalyzing a specific round of chain elongation. An adjacent gene encodes a pipecolate-incorporating enzyme, which completes the macrocycle. The total of 70 constituent active sites makes this the most complex multienzyme system identified so far. The DNA region sequenced (107.3 kbp) contains 24 additional open reading frames, some of which code for proteins governing other key steps in rapamycin biosynthesis.
Researchers ; Professionals ; Students
http://hdl.handle.net/10993/12403

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