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Medicinal microbe Streptomyces coelicolor is sequenced


Scientists have sequenced one of medicine's most important microbes, the bacterium Streptomyces coelicolor. It belongs to a family of bacteria—known as streptomycetes—that produces most of the natural antibiotics in use today, including tetracycline and erythromycin; streptomycetes also produce natural anti-cancer and immune-suppressing compounds. The S. coelicolor sequence is a new tool for researchers trying to develop pharmaceuticals through the genetic engineering of bacteria.

Streptomyces coelicolor colonies with aerial mycelium and spores. The blue haloes around the colonies are secreted actinorhodin. Actinorhodin is an antibiotic (not used clinically) which is blue under alkaline conditions and red under acidic conditions.

Streptomycetes are ubiquitous soil bacteria, and they play a key role in the global carbon cycle by degrading the insoluble remains of other organisms. Streptomyces coelicolor has a large collection of enzymes and can metabolize many diverse nutrients. The microbe is hardy enough to survive significant changes in temperature, water, and food sources.

David A. Hopwood, of the John Innes Centre in Norwich, U.K., and colleagues used the clone-by-clone approach to sequence Streptomyces coelicolor A3(2), which is genetically the best-known representative of the genus. The sequencing was done at the Wellcome Trust Sanger Institute in Cambridge, U.K.

With 8.6 million base pairs, the S. coelicolor genome is one of the largest sequenced bacterial genomes. Of the 7,825 genes, an unprecedented proportion carries out regulatory functions in the cell. More than twelve percent of the genome are involved in facilitating biological processes, such as the bacterium's response to environmental stimuli and stress.

Detail from circular representation of the Streptomyces coelicolor chromosome. View full

The genome structure consists of a linear core chromosome and a pair of chromosome arms. Most of the genes thought to be essential, such as those for cell division and DNA replication, reside in the central core. Genes for non-essential functions, such as secondary metabolites, are found in the arms, according to the researchers.

"The abundance of previously uncharacterized metabolic enzymes, particularly those likely to be involved in the production of natural products, is a resource of enormous potential value," the researchers write in Nature. "Understanding of such enzymes will facilitate the genetic engineering of pathways to produce new compounds with potential therapeutic activity, including much needed antimicrobials."

Streptomycetes are members of the same taxonomic order as the organisms that cause tuberculosis and leprosy, both of which have been sequenced. "Much should be learned about these pathogens from genome-level comparisons with harmless saprophytic relatives such as streptomycetes," the researchers write.

See related GNN article
»Antibiotics from a microbe

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Bentley, S.D. et al. Complete genome sequence of the model actinomycete Streptomyces coelicolor A3(2). Nature 417, 141-147 (May 9, 2002).

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