The rapamycin gene cluster is an example of a gene cluster which includes
a gene (rapL) leading to the formation of a precursor compound (pipecolic
acid, in this case) which is required for inclusion in the larger product
(rapamycin) produced by the enzymes encoded by the cluster. We have
produced a mutant strain containing a rapamycin gene cluster in which the
rapL gene is disabled. The strain does not naturally produce rapamycin
but does so if fed with pipecolic acid. By feeding with alternative
carboxylic acids we have produced variants of rapamycins. Tests have
shown biological activity.