Original Article

The Journal of Antibiotics (2007) 60, 13–19; doi:10.1038/ja.2007.2

Effects of Halogens on the Production of Salinosporamides by the Obligate Marine Actinomycete Salinispora tropica

Kin S Lam1, Ginger Tsueng1, Katherine A Mcarthur1, Scott S Mitchell1,†, Barbara C M Potts1 and Jianlin Xu1,††

1Nereus Pharmaceuticals, Inc., 10480 Wateridge Circle, San Diego, CA 92121, USA

Correspondence: K. S. Lam, Nereus Pharmaceuticals, Inc., 10480 Wateridge Circle, San Diego, CA 92121, USA. E-mail: rlam@nereuspharm.com

†Present address: Gilead Sciences, 333 Lakeside Drive, Foster City, CA 94404

††Present address: Bristol-Myers Squibb, PO Box 4755, Syracuse, NY 13221

Received 25 August 2006; Accepted 4 December 2006.

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Abstract

We examined the effects of halogens on the production of salinosporamide A (NPI-0052) by the obligate marine actinomycete Salinispora tropica NPS465, specifically the production of analogs containing halogens other than chlorine. Adding NaF, NaBr and NaI directly to the production medium prepared in seawater containing ~3% NaCl did not induce the production of the corresponding analogs. Replacing seawater with 2~3% NaI in the production medium enhanced the production of NPI-0052 by 2.1 fold. Replacing seawater with 2~3% NaBr in the production medium suppressed the production of NPI-0052 but induced the production of a brominated analog at very low yield. Using a stepwise enrichment of bromide in the seed cultures in order to reduce the chloride ion carried over to the production medium, the production of the brominated analog was enhanced by 4 fold. We also demonstrated that the growth of this obligate marine actinomycete is dependent upon sodium concentration, not chloride concentration.

Keywords:

NPI-0052, salinosporamide A, Salinispora tropica, marine actinomycete, halogens

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