Industrial Biotransformations

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1 History of Industrial Biotransformations – Dreams and Realities
long reaction time. Furthermore, hazardous reagents, such as phosporus pentachloride,
nitrosyl chloride and pyridine are used in this process and the subsequent removal of
such reagents causes significant problems. Therefore, the development of an enzymatic
process was a dream for a long time. In the enzymatic process, liberated glutaric acid
reduces the pH and inhibits glutaryl-7-ACA amidase, the enzyme that catalyzes the deacylation
of cephalosporin C. Because of this change in pH the reaction rate is decreased,
necessitating strict pH control during the reaction process. For these reasons, a recircu-
Fig. 1.29 Bioreactor plant for the production of 7-ACA carried out at
Asahi Chemical Industry (reprinted from Ref. [71], p. 83, courtesy of
Marcel Dekker Inc.).