This week in techniques



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Drug platforms

Transformation-associated recombination (TAR)-based method to capture large, biosynthetic bacterial gene clusters

A TAR-based approach to isolate bacterial gene clusters could aid the synthesis of natural products including antibiotics. In yeast, TAR was used to assemble a contiguous 67 kb region from the marine actinomycete Saccharomonospora sp. that contained 20 transcriptionally silent open reading frames including a biosynthetic gene cluster. Subsequent deletion of an inhibitory gene, heterologous expression in a model biosynthetic host and structural characterization identified the cluster's product as taromycin A, an antibiotic similar to Cubicin daptomycin. Next steps include streamlining the TAR-based approach for high throughput screening of biosynthetic microbial gene clusters.
Cubist Pharmaceuticals Inc. markets Cubicin to treat bacteremia and skin and skin structure infections.

SciBX 7(6); doi:10.1038/scibx.2014.187
Published online Feb. 13, 2014

Patent application filed; available for licensing from the University of California, San Diego
Contact: Dominic Montisano, University of California, San Diego, La Jolla, Calif.

Yamanaka, K. et al. Proc. Natl. Acad. Sci. USA; published online Jan. 21, 2014;
Contact: Bradley S. Moore, University of California, San Diego, La Jolla, Calif.