Industrial Biotransformations

Penicillin amidase
Escherichia coli
H 2N
O
1) Reaction conditions
[1]: 0.042 M, 10 g · L –1 [238.24 g · mol –1 ]
[2]: 0.063 M, 10.5 g · L –1 [166.17 g · mol –1 ]
pH: 6.0
T: 28 °C
medium: aqueous
reaction type: carboxylic acid amide hydrolysis
catalyst: immobilized enzyme
enzyme: penicillin amidohydrolase (penicillin acylase, gen G amidase)
strain: Escherichia coli
CAS (enzyme): [9014-06-06]
2) Remarks
N
COOH
● The chemical resolution of the racemic azetidinone gives low yields.
● It was thought that the pen G amidase would exhibit only a limited substrate spectrum, since
it does not hydrolyze the phenoxyacetyl side chain of penicillin V. Nevertheless the Lilly process
shows that the pen G amidase acylates the 3-amino function with the methyl ester of phenoxyacetic
acid.
● The acylation occurs using methyl phenylacetate (MPA) or methyl phenoxyacetate (MPOA) as
the acylating agents.
● The enzyme displays similiar enantioselectivity with MPA or MPOA. It is immobilized on
Eupergit (Röhm GmbH, Germany).
3) Flow scheme
Not published.
O
EC 3.5.1.11
[(2R,3S),(2S,3R)]-1 2
(2R,3S)-3
1 = cis-3-amino-azetidinone
2 = phenoxy-acetic acid methyl ester
3 = β-lactam intermediate Eli Lilly
Fig. 3.5.1.11 – 1
+
O COOMe
E
-MeOH
O
O
H
N
O
N
COOH
O
393