Complete genome sequence of the model actinomycete Streptomyces coelicolor A3(2)

Abstract

Streptomyces coelicolor is a representative of the group of soil-dwelling, filamentous bacteria responsible for producing most natural antibiotics used in human and veterinary medicine. Here we report the 8,667,507 base pair linear chromosome of this organism, containing the largest number of genes so far discovered in a bacterium. The 7,825 predicted genes include more than 20 clusters coding for known or predicted secondary metabolites. The genome contains an unprecedented proportion of regulatory genes, predominantly those likely to be involved in responses to external stimuli and stresses, and many duplicated gene sets that may represent 'tissue-specific' isoforms operating in different phases of colonial development, a unique situation for a bacterium. An ancient synteny was revealed between the central 'core' of the chromosome and the whole chromosome of pathogens Mycobacterium tuberculosis and Corynebacterium diphtheriae. The genome sequence will greatly increase our understanding of microbial life in the soil as well as aiding the generation of new drug candidates by genetic engineering.

Genome plasticity and systems evolution in Streptomyces

“…The large number of regulatory proteins that govern the gene expression in a temporal- and spatial-specific manner underscores this capability. It was reported that 965 regulation-related proteins are in the S. coelicolor genome, accounting for about 12% of the ORFs [3]. Our comparative analysis revealed that 263 gene families in the core genome are related to DNA-dependent regulation of transcription (GO:0006355), 201 of which may have sequence-specific DNA binding transcription factor activity (GO:0003700) and 43 families could have specific transcriptional repressor activity (GO:0016566).…”

“…Moreover, 303 gene families in the core genome are predicted to have transfersase activity (GO:0016740), constituting the most abundant class of the enzymes in the core genome. These statistics reflect the most distinctive characteristics of streptomycetes: a powerful biochemical machinery with a magnitude unusually large number for biosynthesis and biotransformation [3]. Table 2 lists examples of functional categories in the core genome critical for Streptomyces biology.…”

“…Streptomycetes are characterized by a large linear chromosome, a rich repertoire of secondary metabolites, and a complex life cycle alternating between the filamentous vegetative mycelium stage and the spore-bearing aerial hyphae stage. They are best known for their importance in medicine and pharmaceuticals, as their secondary metabolic pathways produce more than half of the bioactive compounds in use, including antibiotics, anticancer agents, antiparasitic drugs, antifungals, immunosuppressants, and herbicides [2,3]. They also play a crucial role in maintaining the balance of the biosphere by decomposing the insoluble remains of other organisms such as lignocellulose and chitin.…”

“…The deciphering of the genetic code of S. coelicolor , the best studied organism in Streptomyces in 2002 has opened an unprecedented opportunity for systems-wide explorations of cellular components and their interactions [3]. Genome sequencing revealed an exceptional abundance of gene clusters related to antibiotic reproduction, transcriptional regulation and transport.…”

“…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].…”