Patent ID: 7018808

Claim:
A process for producing an analogue of rapamycin in which an L-pipecolate moiety is substituted by a moiety derived from a precursor compound selected from the group consisting of L-proline, L-trans-4-hydroxyproline, L-cis-4-hydroxyproline, L-cis-3-hydroxyproline and trans-3-aza-bicyclohexane-2-carboxylic acid, said process comprising: a) a step of modifying the gene cluster for the production of rapamycin in a host microorganism, wherein said microorganism is S. hygroscopicus , said gene cluster including a gene, said gene being the rap L gene which encodes the enzyme which is responsible for the production of L-pipecolate which is incorporated into rapamycin, said step comprising the step of deleting or inactivating said rap L gene; and b) a step of culturing said host microorganism in the presence of said precursor compound to effect synthesis of said analogue of raparnycin, whereby said precursor compound is incorporated in said synthesis and said rapamycin analogue is produced.