Optimization of production of monacolin K from γ-irradiated Monascus mutant by use of response surface methodology

Monascus isolate number 711, which is capable of producing monacolin K as an inhibitor of 3-hydroxy-3-methylglutaryl- coenzyme A reductase, the key enzyme of cholesterol synthesis, was isolated from Ang-kak, the red yeast rice koji. To increase the monacolin K-producing activity of the strain, spore suspensions of the strain were subjected to gamma-irradiation. One thousand mutants were generated via gamma-irradiation and screened using bioassay and high performance liquid chromatography analysis. Several mutants with higher productivities of monacolin K than that of the parent strain were primarily selected. Mutant KU609 was finally selected because of its characteristics of high monacolin K production and non-citrinin-producing activity under our test conditions. Response surface methodology was used to analyze the effect of culture medium on the production of monacolin K in mixed solid-state cultures. The optimal values of nutritional ingredients for the maximal production were soytone, glucose, MgSO4, and barley at concentrations of 0.5 g, 0.48 g, 0.053 g, and 9 g, respectively. The final monacolin K production of Monascus KU609 was increased almost 100-fold compared to that of the parent strain.