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

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.