Equilibrium position, kinetics, and reactor concepts for the adipyl-7-ADCA-hydrolysis process

One of the building blocks of cephalosporin antibiotics is 7-amino-deacetox ycephalosporanic acid (7-ADCA). It is currently produced from penicillin G using an elaborate chemical ring-expansion step followed by an enzyme-catal yzed hydrolysis. However, 7-ADCA-like components can also be produced by di rect fermentation. This is of scientific and economic interest because the elaborate ring-expansion step is performed within the microorganism. In thi s article, the hydrolysis of the fermentation product adipyl-7-ADCA is stud ied. Adipyl-7-ADCA can be hydrolyzed in an equilibrium reaction to adipic acid a nd 7-ADCA using glutaryl-acylase. The equilibrium reaction yield is describ ed as a function of pH, temperature, and initial adipyl-7-ADCA concentratio n. Reaction rate equations were derived for adipyl-7-ADCA-hydrolysis using three (pH-independent) reaction rate constants and the apparent equilibrium constant. The reaction rate constants were calculated from experimental da ta. Based on the equilibrium position and re action rate equations the hydr olysis reaction was optimized and standard reactor configurations were eval uated. It was found that equilibrium yields are high at high pH, high tempe rature and low-initial adipyl-7-ADCA concentration. The course of the react ion could be described well as a function of pH (7-9), temperature (20-40 d egreesC) and concentration using the reaction rate equations. It was shown that a series of CSTR's is the best alternative for the process. (C) 2000 J ohn Wiley & Sons, Inc.