Production of ML-236B, and Inhibitor of 3-Hydroxy-3-methylglutaryl CoA Reductase, by Penicillium citrinum: Improvements of Strain and Culture Conditions

• Published in: Bioscience, biotechnology, and biochemistry Vol. 57; no. 9; pp. 1414 - 1419
• Main Authors: Hosobuchi, Masahiko, Shioiri, Tetsuya, Ohyama, Jo, Arai, Masatoshi, Iwado, Seigo, Yoshikawa, Hiroji
• Format: Journal Article
• Language: English
• Published: Tokyo Taylor & Francis 1993; Japan Society for Bioscience Biotechnology and Agrochemistry
• Subjects: Biological and medical sciences; Biotechnology; Fundamental and applied biological sciences. Psychology; Health. Pharmaceutical industry; Industrial applications and implications. Economical aspects; Other active biomolecules; Penicillium citrinum; Production of active biomolecules; Fungi; Enzyme; Process improvement; Production; Enzyme inhibitor; Hydroxymethylglutaryl-CoA reductase; Biosynthesis; Fungi Imperfecti; Oxidoreductases; Precursor; Penicillium citrinum; Thallophyta
• ISSN: 0916-8451; 1347-6947
• DOI: 10.1271/bbb.57.1414

In order to increase the yield of ML-236B, an intermediate for pravastatin Na (an inhibitor of cholesterol synthesis) production, the improvements of an ML-236B producing strain of Penicillium citrinum, the medium composition, and the culture conditions were studied. A mutant strain S-5808, which produces ML-236B 20 times more than the original strain does in flask culture, was isolated. As the cells of S-5808 required a large amount of the carbon source substrate to produce a lot of ML-236B, a fed-batch culture method was developed. The continuous feeding of carbon source (glycerol or mixture of glycerol and maltose) was very effective for the increase of ML-236B production.
ML-236B in the culture broth became oily with lowering of pH during cultivation, adhered to the cell surface, decreased the carbon source consumption and finally stopped the ML-236B production at a late period of fermentation. The addition of a polypropylene glycol type surfactant enhanced the ML-236B productivity. The addition of the surfactant released oily ML-236B from the cell surface, therefore oxygen uptake, carbon source consumption, and ML-236B production continued throughout the fermentation.