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Isolation and Characterization of Pre‐rapamycin, the First Macrocyclic Intermediate in the Biosynthesis of the Immunosuppressant Rapamycin by S. hygroscopicus
Author(s) -
Gregory Matthew A.,
Gaisser Sabine,
Lill Rachel E.,
Hong Hui,
Sheridan Rose M.,
Wilkinson Barrie,
Petkovic Hrvoje,
Weston Alison J.,
Carletti Isabelle,
Lee HuaiLo,
Staunton James,
Leadlay Peter F.
Publication year - 2004
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.200453764
Subject(s) - streptomyces hygroscopicus , complementation , gene cluster , strain (injury) , gene , biosynthesis , biology , chemistry , computational biology , biochemistry , streptomyces , genetics , bacteria , phenotype , anatomy
It's a rap : A double recombination strategy has been utilized to uncover the biosynthetic route to the key intermediate in the formation of rapamycin. Removal of a section of the rapamycin gene cluster from Streptomyces hygroscopicus produced a strain that generated no rapamycin. Gene complementation proved, surprisingly, that the accumulation of this previously elusive intermediate pre‐rapamycin ( 1 ) depended on the presence of the gene rapK.