Industrial Biotransformations

Leucine dehydrogenase
Bacillus sphaericus
4) Process parameters
yield: 74 %
reactor type: repetitive batch with ultrafiltration (enzyme membrane reactor)
capacity: ton scale
residence time: 2 h
space-time-yield: 638 g · L –1 ·d –1
down stream processing: crystallization
enzyme consumption: leucine dehydrogenase: 0.9 U · g –1 , formate dehydrogenase: 2.3 U · g –1
company: Degussa AG, Germany
5) Product application
● The amino acids are building blocks for drug synthesis, e.g. anti-tumor agents or HIV protease
inhibitors.
● They can also be used as templates in asymmetric synthesis:
H
N
R
HO
N
N
Ph OH
O
O
N
H
H
N
HO
N
OH
O
O
H
O
H
N
1
3
5
O
H
N
H
N
O
Ph
CH 3
Ph OH
1 = Sandoz (antiviral)
2 = Biomega (antiviral)
3 = BB-25 16 (antitumor)
4 = RO-31-9790 (antiinflammatory)
5 = Abbott (antiviral)
6 = Zeneca (antitumor)
7 = tert.-leucine
Fig. 1.4.1.9 – 5
NH
Ph
N
H
R
O O N
NH2
L-7
COOH
HN
O
O
N
H
N
O
N
H
O
O
HN OH
N
O
H
N
CH 2CN
2
O
F
4
6
H
N
O
O
N
H
COOH
O
N
H
EC 1.4.1.9
H
N
COOH
CH 3
COOH
205