title: Defined salt formulations for the growth of Salinispora tropica strain NPS21184 and the production of salinosporamide A (NPI-0052) and related analogs.
abstract: Salinosporamide A (NPI-0052) is currently produced by a marine actinomycete, Salinispora tropica, via a saline fermentation process using a non-defined, commercially available synthetic sea salt, Instant Ocean. In order to control the consistency of the production of NPI-0052 and related analogs, two chemically defined salt formulations were developed to replace Instant Ocean. A chemically defined sodium-chloride-based salt formulation with similar sodium and chloride contents as in Instant Ocean was found to support higher production of NPI-0052 and a better metabolite production profile for downstream processing than Instant Ocean. A chemically defined sodium-sulfate-based salt formulation with low chloride concentration at 17 mM was found to support a similar NPI-0052 and metabolite production profile as Instant Ocean. The sodium-sulfate-based formulation is a robust formulation for large-scale production process due to its reduced corrosiveness in fermentation as compared with the saline fermentation utilizing Instant Ocean or the sodium-chloride-based salt formulation. The production of NPI-0052 in both chemically defined salt formulations was successfully scaled-up to a 42-l fermentor, indicating that these salt formulations can be used for large-scale manufacturing process.
authors.affiliation: Nereus Pharmaceuticals, Inc., 10480 Wateridge Circle, San Diego, CA 92121, USA.
authors.forename: Ginger
authors.initials: G
authors.lastname: Tsueng
authors.forename: Sy
authors.initials: S
authors.lastname: Teisan
authors.forename: Kin S
authors.initials: KS
authors.lastname: Lam
mesh_terms: D003470:Culture Media / Q000737:chemistry*; D019015:Geologic Sediments / Q000382:microbiology; D007218:Industrial Microbiology; D007783:Lactones / Q000737:chemistry / Q000378:metabolism*; D013058:Mass Spectrometry; D008848:Micromonosporaceae / Q000254:growth & development / Q000378:metabolism*; D011758:Pyrroles / Q000737:chemistry / Q000378:metabolism*; D012965:Sodium Chloride / Q000032:analysis / Q000378:metabolism*
chemical_list: D003470:Culture Media; D007783:Lactones; D011758:Pyrroles; D012965:Sodium Chloride; C475865:marizomib