Streptomyces avermitlis has a life cycle with complex morphological differentiation and the ability to produce many secondary metabolites, one of which, avermectin, is commercially important in human and veterinary medicine. The major interest of the genus Streptomyces is the diversity of the production of secondary metabolites as an industrial microorganism. We have determined ca. 99% of the genome of S. avermitilis ATCC31267. The genome is composed of about 8.7 million base pairs in linear chromosome, that is the largest bacterial genome sequences, and provides insights into intrinsic diversity of the secondary metabolite production in Streptomyces. Twenty-five kinds of secondary metabolite gene clusters were found in the genome of S. avermitlis. Total length of these clusters occupies about 6.4% of the genome. A locus of pte gene cluster contained genes for five type-I modular polyketide synthases (PKSs) and postpolyketide modification enzymes. These PKSs consisted of 13 modules carrying 57 catalytic domains. In consideration of organization of domains in each module, five PKSs would catalyze to make 26-membered macrocyclic lactone with five conjugated double bonds that is a pentaene compound.