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Developing a new resource for drug discovery: marine actinomycete bacteria

Nature Chemical Biology volume 2, pages 666–673 (2006)Cite this article

Abstract

Natural products are both a fundamental source of new chemical diversity and an integral component of today's pharmaceutical compendium. Yet interest in natural-product drug discovery has waned, in part owing to diminishing returns from traditional resources such as soil bacteria. The oceans cover 70% of the Earth's surface and harbor most of the planet's biodiversity. Although marine plants and invertebrates have received considerable attention as a resource for natural-product discovery, the microbiological component of this diversity remains relatively unexplored. Recent studies have revealed that select groups of marine actinomycetes are a robust source of new natural products. Members of the genus Salinispora have proven to be a particularly rich source of new chemical structures, including the potent proteasome inhibitor salinosporamide A, and other distinct groups are yielding new classes of terpenoids, amino acid–derived metabolites and polyene macrolides. The continued development of improved cultivation methods and technologies for accessing deep-sea environments promises to provide access to this significant new source of chemical diversity.

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Figure 1: Radial tree depicting the phylogenetic relationships of 13 groups of marine-derived actinomycetes within six different families.
Figure 2: Structures and biosynthesis of metabolites from Salinispora tropica.
Figure 3: Representations, based on X-ray data, of the CT-L active site of the yeast 20S proteasome complexed with salinosporamide A (Sal A).
Figure 4
Figure 5: Representative structures (15, 16 and 17) of the numerous polyene-polyol antibiotics produced by the Marinispora group.
Figure 6: Structures of the antibiotic abyssomycin C (23) and the anticancer drug candidate thiocoraline (24).

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Acknowledgements

We thank the US National Institutes of Health, National Cancer Institute for generous continuing support of this research under grants CA44848, CA052955 and CA048112. Support from the NCI allowed the unusual marine microbiology described herein to be explored. We thank V. Bernan (Wyeth Research Laboratories) for S. pacifica sequence data.

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  1. the Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California, San Diego, La Jolla, 92093-0204, California, USA

    William Fenical & Paul R Jensen

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Correspondence to William Fenical.

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W.F. and P.J. are founders of and consultants to Nereus Pharmaceuticals.

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Fenical, W., Jensen, P. Developing a new resource for drug discovery: marine actinomycete bacteria. Nat Chem Biol 2, 666–673 (2006). https://doi.org/10.1038/nchembio841

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