Fuzzy control in microbial production of ML-236B, a precursor of pravastatin sodium

Abstract Fuzzy control was applied to the fermentation of ML-236B by Penicillium citrinum. In order to maintain the pH of the culture at a suitable level for ML-236B production (pH 3.7 to 3.9), a computer aided system using fuzzy control was designed for controlling the feed rate of sugar. Membership functions and fuzzy rules were constructed based on analysis of the knowhow and the rules obtained from skilled operators. The fuzzy clusterization method for the culture phase and Sugeno's inference method III for defuzzyfication were incorporated into the fuzzy control algorithm. Using this fuzzy control method, it was possible to maintain the pH within the range of 3.90 to 3.95. From the relationship between pH (3.3 to 4.3) and ML-236B productivity, cultures with a pH value from 3.7 to 3.9 yielded the highest ML-236B productivity. ML-236B production was 10% higher using fuzzy control than when using manual control.