Industrial Biotransformations

Penicillin acylase
Escherichia coli
N
R
COOH
3
R
O +
O
- R2H
1 R1 1) Reaction conditions
medium: aqueous
reaction type: carboxylic acid amide hydrolysis
catalyst: immobilized whole cells or enzyme
enzyme: penicillin amidase (penicillin amidase, α-acylamino-β-lactam acylhydrolase)
strain: Escherichia coli and others
CAS (enzyme): [9014-06-06]
2) Remarks
NH 2
D-(-)-1
R 2
H2N
1a = phenylglycineamide (R1 =H, R2 =NH2) = PGA
1b = phenylglycinemethylester (R1 =H, R2 =OMe) = PGM
1c = hydroxyphenylglycineamide (R1 =OH, R2 =NH2) = HPGA
1d = hydroxyphenylglycinemethylester (R1 =OH, R2 =OMe) = HPGM
2a = 7-aminodeacetoxycephalosporanic acid (R3 =Me) = 7-ADCA
2b = 7-aminodeacetoxymethyl-3-chlorocephalosporanic acid (R3 =Cl) = 7-ACCA
3a = cefaclor (R1 =H, R3 =Cl)
3b = cephalexin (R1 =H, R3 =Me)
3c = cefadroxil (R1 =OH, R3 =Me)
Fig. 3.5.1.11 – 1
2
S
EC 3.5.1.11
● The established chemical synthesis started from benzaldehyde and included fermentation of
penicillin G. The process consisted of ten steps with a waste stream of 30–40 kg waste per kg
product. The waste contained methylene chloride, other solvents, silylating agents and many
by-products from side chain protection and acylating promoters.
● In comparison, the chemoenzymatic route needs only six steps including three biocatalytic
ones.
● The following figure compares the chemical and chemo-enzymatic routes (Bruggink, 1996):
E
NH2
O
3
H
N
O
N
S
COOH
R 3
DSM
397