Cgph. Schroen et al., Equilibrium position, kinetics, and reactor concepts for the adipyl-7-ADCA-hydrolysis process, BIOTECH BIO, 70(6), 2000, pp. 654-661
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.