Soil Bacteria As a Rich Source of Enediyne Antibiotics and Anti-Cancer Compounds

Following the screening of more than 3,400 different actinomycete (soil bacteria) isolates, researchers have isolated several powerful new antibiotics and potential anti-cancer compounds.

Investigators at The Scripps Research Institute (Jupiter, FL, USA) surveyed the genomes of some 3,400 actinomycetes, identifying 81 strains that harbored genes encoding the enediyne polyketide synthase family of enzymes.

The enediyne polyketides are secondary metabolites isolated from a variety of Actinomycetes. All members share very potent anti-cancer and antibiotic activity. The biosynthesis of these compounds is of interest because of the numerous structural features that are unique to the enediyne family. The gene cluster for five enediynes has now been cloned and sequenced, providing the foundation to understand natures’ means to biosynthesize such complex, exotic molecules.

A macromolecular antibiotic C-1027 had been obtained previously from the broth filtrate of Streptomyces globisporus by precipitation with ammonium sulfate, DEAE-cellulose column chromatography, and gel filtration chromatography on a Sephadex G-75 column.

In the current study, the investigators identified new C-1027 producers, with a significantly higher C-1027 titer than the original producer, and discovered a new family of enediyne natural products, the tiancimycins (TNMs), that exhibited potent cytotoxicity against a broad spectrum of cancer cell lines.

"The enediynes represent one of the most fascinating families of natural products for their extraordinary biological activities," said senior author Dr. Ben Shen, professor of chemistry at The Scripps Research Institute. "By surveying 3,400 strains from the The Scripps Research Institute collection, we were able to identify 81 strains that harbor genes encoding enediynes. With what we know, we can predict novel structural insights that can be exploited to radically accelerate enediyne-based drug discovery and development."

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