Complete genome sequence and comparative analysis of the industrial microorganism Streptomyces avermitilis

Abstract

Species of the genus Streptomyces are of major pharmaceutical interest because they synthesize a variety of bioactive secondary metabolites. We have determined the complete nucleotide sequence of the linear chromosome of Streptomyces avermitilis. S. avermitilis produces avermectins, a group of antiparasitic agents used in human and veterinary medicine. The genome contains 9,025,608 bases (average GC content, 70.7%) and encodes at least 7,574 potential open reading frames (ORFs). Thirty-five percent of the ORFs (2,664) constitute 721 paralogous families. Thirty gene clusters related to secondary metabolite biosynthesis were identified, corresponding to 6.6% of the genome. Comparison with Streptomyces coelicolor A3(2) revealed that an internal 6.5-Mb region in the S. avermitilis genome was highly conserved with respect to gene order and content, and contained all known essential genes but showed perfectly asymmetric structure at the oriC center. In contrast, the terminal regions were not conserved and preferentially contained nonessential genes.

Genome plasticity and systems evolution in Streptomyces

“…The master regulators of critical importance in streptomycetes include a set of sigma factors which serve as transcription initiation factors, enabling specific binding of RNA polymerase to the promoter region of target genes. S. coelicolor and S. aveimitilis both have over 60 sigma factors [3,6], outnumbering most of the bacteria which generally have < 20 sigma factors. Our analysis identified 31 gene families in the core genome which have putative sigma factor activity (GO:0005525).…”

“…The number of gene clusters for secondary metabolism in the five Streptomyces genomes ranges from 23 to 37 [3,6,19-21,42,43]. As the detailed information for each secondary metabolite gene cluster (i.e., chromosome location and predicted/known product) is yet to be published for S. bingchenggensis , our subsequent discussion is focused on the remaining four genomes.…”

“…Similar examples include avermectin in S. avermitilis , streptomycin in S. griseus , milbemycin in S. bingchenggensis , and thaxtomin and concanamycin, the plant toxins associated with virulence in S. scabiei [27]. Discussions of these gene clusters are detailed in literature [3,6,19,20,42,43] and therefore they will not be repeated here.…”

“…Genome sequencing revealed an exceptional abundance of gene clusters related to antibiotic reproduction, transcriptional regulation and transport. The genome sequence of the second species in this genus, S. avermitilis , an industrial strain for avermectin production, was released in 2003 [6]. At the time of writing, the genome sequencing projects of about 30 Streptomyces strains are in various stages of completion.…”

“…In this study, we report a comprehensive comparative genomic analysis of five model species in the genus Streptomyces [3,6,19-21] with complete genome sequences and annotation [22]: (1) S. coelicolor is a model organism for streptomycetes and it can produce a variety of antibiotics, including actinorhodin, CDA (calcium-dependent antibiotic), methylenomycin, and undecylprodigiosin [23]; (2) S. avermitilis [6] produces avermectin which is a potent agent against a wide array of nematodes and arthropod parasites; (3) S. griseus [20] produces streptomycin, a broad-spectrum antibiotic which has been used for the treatment of various diseases such as tuberculosis and the plague caused by Yersinia pestis [24,25]. It has also served as a model system for the study of "tissue" differentiation as a large body of work has been focused on delineating the regulatory mechanisms of morphological differentiation and tightly linked secondary metabolism [26]; (4) S. bingchenggensis produces milbemycin, an antiparasitic agent against worms, ticks and fleas used in veterinary clinics [19]; (5) S. scabiei [21], unlike the majority of streptomycetes which are non-pathogenic, is the causative agent for potato scab, a disease that is responsible for significant economic losses worldwide [21,27].…”