In large scale saline fermentation of salinosporamide A (NPI-0052) by marine actinomycete Salinispora tropica, the presence of the co-metabolites NPI-0047 and NPI-2065 lowered the recovery yield of NPI-0052.  It has been well documented that trace metal ions have significant impacts on the production of secondary metabolites.  In a preliminary study, we found that cobalt ion has a specific inhibition effect on the production of NPI-0047 and it does not affect the production of NPI-0052.  This is an important finding since we can simply supplement the medium with cobalt ion to lower the production of NPI-0047 without performing any laborious strain improvement program involving genetic engineering of the producing organism.  Using a completely defined sodium chloride-based salt formulation containing cobalt chloride, we reduced the production of NPI-0047 by 91% while the production of NPI-0052 was slightly increased by 13%.  The production of NPI-0047 was only 0.4% of the production of NPI-0052 in the cobalt-supplemented medium.  The production of the other interfering analog, NPI-2065, was also reduced by 14% in the cobalt-supplemented medium.  Further modification of the above salt formulation enabled us to develop methods to increase the production of the minor analogs, such as NPI-2080, by 140-fold.  The effect of cobalt on the production of salinosporamides and the utility of the defined salt formulation in production of minor analogs will be discussed.