Get access

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


  • 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).


original image

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.