Genome sequence of an industrial microorganism Streptomyces avermitilis: Deducing the ability of producing secondary metabolites

Streptomyces avermitilis is a soil bacterium that carries out not only a co mplex morphological differentiation but also the production of secondary me tabolites, one of which, avermectin, is commercially important in human and veterinary medicine. The major interest in this genus Streptomyces is the diversity of its production of secondary metabolites as an industrial micro organism. A major factor in its prominence as a producer of the variety of secondary metabolites is its possession of several metabolic pathways for b iosynthesis. Here we report sequence analysis of S. avermitilis, covering 9 9% of its genome. At least 8.7 million base pairs exist in the linear chrom osome; this is the largest bacterial genome sequence, and it provides insig hts into the intrinsic diversity of the production of the secondary metabol ites of Streptomyces. Twenty-five kinds of secondary metabolite gene cluste rs were found in the genome of S. avermitilis. Four of them are concerned w ith the biosyntheses of melanin pigments, in which two clusters encode tyro sinase and its cofactor, another two encode an ochronotic pigment derived f rom homogentiginic acid, and another polyketide-derived melanin. The gene c lusters for carotenoid and siderophore biosyntheses are composed of seven a nd five genes respectively. There are eight kinds of gene clusters for type -I polyketide compound biosyntheses, and two clusters are involved in the b iosyntheses of type-II polyketide-derived compounds. Furthermore, a polyket ide synthase that resembles phloroglucinol synthase was detected. Eight clu sters are involved in the biosyntheses; of peptide compounds that are synth esized by nonribosomal peptide synthetases. These secondary metabolite clus ters are widely located in the genome but half of them are near both ends o f the genome. The total length of these clusters occupies about 6.4% of the genome.