The complete genome sequence of Streptomyces avermitilis, an industrial microorganism, was determined and compared with that of Streptomyces coelicolor A3(2). The S. avermitilis genome consists of 9,025,608 bases with an average GC content of 70.7% and encodes at least 7,574 potential open reading frames (ORFs). Of these, 35% (2,664) form 721 paralogous families. Thirty-five gene clusters related to secondary metabolite biosynthesis were identified, accounting for 6.6% of the genome. Comparison with S. coelicolor A3(2) revealed a highly conserved 6.5-Mb internal region in the S. avermitilis genome, containing all known essential genes but showing asymmetric structure at the oriC center. In contrast, the terminal regions were not conserved and contained nonessential genes. S. avermitilis is a Gram-positive bacterium that produces avermectins, a group of antiparasitic agents. The genome contains 7,574 ORFs, with 4,563 (60.2%) assigned putative functions. The plasmid SAP1 contains 96 ORFs, with 33 (34.3%) assigned putative functions. The genome also contains 60 putative RNA polymerase sigma factors, with 47 belonging to the extracytoplasmic function (ECF) subfamily. The analysis of the linear genome structure identified a putative origin of replication (oriC) and terminal sequences showing extensive homology with other Streptomyces chromosomes. Comparative analysis with S. coelicolor A3(2) revealed that 5,283 genes have orthologs in S. coelicolor A3(2), while 2,291 genes are unique to S. avermitilis. The genome contains 30 secondary metabolite gene clusters, with 17 located in subtelomeric regions. These clusters include those involved in the biosynthesis of terpene compounds and polyketide compounds. The 6.5-Mb internal region contains most essential genes and shows structural similarity to other circular bacterial chromosomes. The subtelomeric regions contain many mobile elements and non-essential genes, suggesting frequent gene duplication in these regions. The genome analysis suggests that S. avermitilis has evolved by acquiring novel gene functions to adapt to its environment. The study provides valuable information for understanding the genetic features of Streptomyces and their potential applications in industrial fields, including drug discovery. The complete genome sequence and comparative analysis of S. avermitilis will aid in improving and modifying the organism for the production of secondary metabolites, including antibiotics.The complete genome sequence of Streptomyces avermitilis, an industrial microorganism, was determined and compared with that of Streptomyces coelicolor A3(2). The S. avermitilis genome consists of 9,025,608 bases with an average GC content of 70.7% and encodes at least 7,574 potential open reading frames (ORFs). Of these, 35% (2,664) form 721 paralogous families. Thirty-five gene clusters related to secondary metabolite biosynthesis were identified, accounting for 6.6% of the genome. Comparison with S. coelicolor A3(2) revealed a highly conserved 6.5-Mb internal region in the S. avermitilis genome, containing all known essential genes but showing asymmetric structure at the oriC center. In contrast, the terminal regions were not conserved and contained nonessential genes. S. avermitilis is a Gram-positive bacterium that produces avermectins, a group of antiparasitic agents. The genome contains 7,574 ORFs, with 4,563 (60.2%) assigned putative functions. The plasmid SAP1 contains 96 ORFs, with 33 (34.3%) assigned putative functions. The genome also contains 60 putative RNA polymerase sigma factors, with 47 belonging to the extracytoplasmic function (ECF) subfamily. The analysis of the linear genome structure identified a putative origin of replication (oriC) and terminal sequences showing extensive homology with other Streptomyces chromosomes. Comparative analysis with S. coelicolor A3(2) revealed that 5,283 genes have orthologs in S. coelicolor A3(2), while 2,291 genes are unique to S. avermitilis. The genome contains 30 secondary metabolite gene clusters, with 17 located in subtelomeric regions. These clusters include those involved in the biosynthesis of terpene compounds and polyketide compounds. The 6.5-Mb internal region contains most essential genes and shows structural similarity to other circular bacterial chromosomes. The subtelomeric regions contain many mobile elements and non-essential genes, suggesting frequent gene duplication in these regions. The genome analysis suggests that S. avermitilis has evolved by acquiring novel gene functions to adapt to its environment. The study provides valuable information for understanding the genetic features of Streptomyces and their potential applications in industrial fields, including drug discovery. The complete genome sequence and comparative analysis of S. avermitilis will aid in improving and modifying the organism for the production of secondary metabolites, including antibiotics.