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.
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. |