Use of a genetic algorithm in the development of a synthetic growth medium for Arthrobacter simplex with high hydrocortisone Δ1‐dehydrogenase activity

The production process for Arthrobacter simplex with high specific hydrocortisone Δ 1 -dehydrogenase activity was improved by medium optimization in parallel shake flask experiments. Using a genetic algorithm, the concentrations of 12 medium components (mineral salts and amino acid) were optimized within 144 experiments to give maximum specific hydrocortisone Δ 1 -dehydrogenase activity and biomass yield (full experimental plan : 1.5 x10 14 experiments). The specific hydrocortisone Δ 1 -dehydrogenase activity was improved by a factor of 4.5 to 1800 U g -1 . With the optimized medium composition in a stirred tank reactor for batch production of A. simplex, a specific hydrocortisone Δ 1 -dehydrogenase activity of 2000-3000 U g -1 dry biomass was achieved depending on harvest time (previously reported data : 18-37 U g -1 ).