Production of doramectin by rational engineering of the avermectin biosynthetic pathway.

In an attempt to construct a strain that produces doramectin, the loading module of Ave polyketide synthase (PKS) from Streptomyces avermitilis M1 was replaced with a cyclohexanecarboxylic (CHC) unique loading module from phoslactomycin PKS. Additionally, the CHC-CoA biosynthetic gene cassette was introduced into the engineered strain, which provided the precursor for directed biosynthesis of doramectin. The doramectin production ability of the final mutant S. avermitilis TG2002 was increased about six times and the ratio of Dor to Ave was enhanced 300 times more than the original strain.