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Mutasynthesis of Rapamycin Analogues through the Manipulation of a Gene Governing Starter Unit Biosynthesis

Authors


  • We thank Dr. Jens Fuchser and Dr. Matthias Witt (Bruker Daltonik GmbH, Bremen (Germany)) and Dr. Paul Gates (University of Cambridge) for help with FT-ICR-MS experiments, and Dr. Apoorva Bhatt for helpful discussions. Work carried out in Cambridge was supported by a project grant from the BBSRC (UK).

Abstract

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The surprising discovery has been made that the gene product RapK is required for production of the starter unit in the rapamycin polyketide cluster. It is shown that a deletion mutant (Streptomyces hygroscopicus MG2–10) provides a clean background for the mutasynthesis of pre-rapamycin (the precursor to rapamycin, see structure) when fed with novel starter units.

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