Carbon and complex nitrogen source selection for secondary metabolite cultivation at the pilot scale.
The fermentation of desmethyl-asterriquinone B-1, a diabetes target, by a Pseudomonasarias species was conducted at the 600-l scale using a revised complex medium containing yeast extract and soy hydrolysate. Oat flour and tomato paste were removed from this medium due to difficulties in sterilization. An initial cerelose charge of 40 g/l improved titer and reduced product degradation in the broth at cultivation conditions. An initial mannitol concentration of 65 g/l effectively avoided mid-cycle mannitol additions necessary for the 40 g/l mannitol concentration without the reduction in productivity seen at 90 g/l mannitol. These additions diluted the broth because of the low aqueous solubility of mannitol. Titers reached 3.0 g/l after 158 h with an optimized process, increasing two-fold from the original medium and operating conditions. Reproducible foaming occurred at the point of glucose exhaustion when the culture switched to mannitol consumption. Use of alternative carbon sources (glycerol, soybean oil, sorbitol in conjunction with cerelose) was not effective in attaining similar productivity and did not reduce the extent of foaming. In the case of fructose, the extent of foaming was markedly reduced but product formation was negligible.
Junker
B
B
Bioprocess Research and Development, Merck Research Laboratories, Rahway, NJ, USA. beth_junker@merck.com
Mann
Z
Z
Burgess
B
B
King
J
J
Greasham
R
R