MORPHOLOGY CONTROL OF PRECULTURE DURING PRODUCTION OF ML-236B, A PRECURSOR OF PRAVASTATIN SODIUM, BY PENICILLIUM-CITRINUM

In order to scale-up the production of ML-236B, a precursor of pravastatin sodium, by Penicillium citrinum H strain, a method for controlling mycelial morphology was developed to increase the number of free mycelia in the preculture process. The use of a high concentration preculture medium (HCP medium) instead of a light medium, MBG3-4 medium, caused the morphology in the preculture broth to change from pellet form to filamentous form. A new preculture process was developed in which HCP medium was used in the third and the fourth precultures. Using this process, the number of free mycelia increased 100-fold and ML-236B production increased 1.5-fold compared to that obtained using the conventional process. It was possible-to stabilize the productivity of ML-236B by inoculating the production culture with a fixed number of free mycelia.