Original Article

The Journal of Antibiotics (2014) 67, 121–126; doi:10.1038/ja.2013.115; published online 13 November 2013

Structure and activity of lobophorins from a turrid mollusk-associated Streptomyces sp

Zhenjian Lin1, Michael Koch2, Christopher D Pond2, Gaiselle Mabeza3, Romell A Seronay3, Gisela P Concepcion3, Louis R Barrows2, Baldomero M Olivera4 and Eric W Schmidt1,4

  1. 1Department of Medicinal Chemistry, L.S. Skaggs Pharmacy Institute, University of Utah, Salt Lake City, UT, USA
  2. 2Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, UT, USA
  3. 3Marine Science Institute, University of the Philippines Diliman, Quezon City, Philippines
  4. 4Department of Biology, University of Utah, Salt Lake City, UT, USA

Correspondence: Professor EW Schmidt, Department of Medicinal Chemistry, The University of Utah, 30 South 2000 East, Room 307, Salt Lake City, UT 84112, USA. E-mail: ews1@utah.edu

Received 29 July 2013; Revised 7 October 2013; Accepted 11 October 2013
Advance online publication 13 November 2013

We are grateful to Professor Christopher Walsh for his inspiring studies of natural products and for his profound impact on the development of our field.

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Abstract

A novel lumun-lumun sampling methodology was used to obtain a large diversity of micromollusks, including the new species Lienardia totopotens. In turn, from L. totopotens we cultivated a Streptomyces sp. strain that contained new and known spirotetronate polyketides, lobophorins (1–5). The structures were elucidated using spectroscopy, and the compounds were evaluated for cytotoxicity to human cells and activity against Mycobacterium tuberculosis, Bacillus subtilis, Pseudomonas aeruginosa and Burkholderia cepacia. Compounds 2–5 showed varying degrees of activity against human cells, M. tuberculosis and B. subtilis in the low μM to mid nM range but were inactive against the other strains, while 1 lacking digitoxose was inactive. Very slight structural changes in 2–5 led to varying antibacterial:cytotoxicity ratios, providing a possible basis to synthesize more selective derivatives.

Keywords:

cone snail; Mycobacterium tuberculosis; Streptomyces