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Antibiotics from a microbe
The genome of an industrial organism
By Birgit Reinert


Japanese researchers have reported the genome sequence of Streptomyces avermitilis, a free-living bacterium that grows in the soil. The bacterium is commercially important for human and veterinary medicine because it is one of the main producers of antibiotics. The sequencing revealed many genes involved in producing natural antibiotics that reside in clusters near both ends of the linear-shaped chromosome. These gene clusters interest researchers because understanding the antibiotic-producing mechanism could help generate novel drugs and slow down antibiotic resistance.

The test to determine antibiotic production. After the Streptomyces isolate has grown for several days, several test organisms are streaked at right angles right up to the Streptomyces growth. Inability of a test organism to grow in the presence of Streptomyces suggests antibiotic production by the latter.

For bacterial standards, S. avermitilis has an unusually large genome of at least 8.7 million base pairs that consists of one linear chromosome. The team of researchers headed by Satoshi Omura, of the Kitasato Institute, in Tokyo, Japan, analyzed 99 percent of the genome using the whole-genome shotgun sequencing method. Altogether, they found at least 7,600 genes. Researchers have attributed the large genome size to extremely variable environmental factors the bacterium has to face as a free-living organism in the soil.

"The most interesting property of Streptomyces is its ability to produce secondary metabolites including antibiotics and bioactive compounds valued in human and veterinary medicine, agriculture, and unique biochemical tools," Omura—a specialist in the chemistry of natural products—and colleagues write in Proceedings of the National Academy of Sciences. Secondary metabolites are compounds with antibacterial, antifungal, and antiviral properties and encompass a large variety of antibiotics. Researchers believe that these metabolites are produced by the bacterium at the end of its vegetative growth.

The scientists identified 25 kinds of gene clusters related to secondary metabolites. Even though these clusters are spread throughout the chromosome, the researchers were surprised to find about half of them located near both ends of the chromosome. "Some of the secondary metabolite clusters might have been horizontally transferred from donor microorganisms in the past," the researchers suggest.

Out of the 25 gene clusters, eight were found to produce compounds called avermectins. Avermectins are among the most important drugs for treating parasitic infections of livestock and humans, according to the researchers. The bacterial strain used in the study is S. avermitilis ATCC31267.

Why Streptomyces produce so many kinds of antibiotics and bioactive compounds is not yet fully understood. "One of the answers," Omura and his team suggest, "is that Streptomyces strains have many gene clusters, which encode enzymes for many secondary pathways."

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Omura, S. et al. Genome sequence of an industrial microorganism Streptomyces avermitilis: Deducing the ability of producing secondary metabolites. Proc Natl Acad Sci USA 98, 12215-12220 (October 9, 2001).

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