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

Kin S. Lam, Ginger Tsueng, Katherine A. McArthur, Scott S. Mitchell, Barbara C. M. Potts, Jianlin Xu††

Received: August 25, 2006 / Accepted: December 4, 2006
© Japan Antibiotics Research Association

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

K. S. Lam (Corresponding author), G. Tsueng, K. A. McArthur, S. S. Mitchell, B. C. M. Potts, J. Xu: 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