Abstract
A continuous production process for formate dehydrogenase (FDH) production by the methylotrophic yeast Candida boidinii was improved by medium optimization in parallel shake-flask experiments. Using a genetic algorithm the concentrations of 14 medium components (trace elements and vitamins) were optimized within 125 experiments to give a maximum FDH activity with minimum use of nutrients salts (full experimental plan: 101 14 experiments!). Employing this optimized medium composition in a 200-litre pilot-scale experiment for continuous methanol-controlled FDH production, a high specific FDH activity of 70 U/g dry cell mass was achieved at a residence time of 15 h. Compared to results with the medium used previously, under the same operating conditions, FDH space-time yield and FDH activity were thus improved by 50% from 100 to 150 U/litre/h and 1550 to 2300 U/litre, respectively.
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