Industrial Biotransformations

Oxygenase
Nocardia autotropica
1) Reaction conditions
[1]: < 0.05 · 10 –3 M, < 0.02 g · L –1 [416.26 g · mol –1 ] (steady state)
[2]: 1.85 · 10 –3 M, 0.8 g · L –1 [432.26 g · mol –1 ]
pH: 6.8
T: 27 °C
medium: aqueous
reaction type: hydroxylation
catalyst: suspended whole cells
enzyme: substrate, reduced-flavoprotein: oxygen oxidoreductase
(unspecific monooxygenase)
strain: Nocardia autotropica
CAS (enzyme): [62213–32–5]
2) Remarks
O
HO
O
O
O
O
H H
+ [O]
1
EC 1.14.14.1
1 = Simvastatin
2 = 6-β-hydroxy-methyl-simvastatin (major product) Merck Sharp & Dohme
Fig. 1.14.14.1 – 1
E
● Due to a strong surplus inhibition, simvastatin is continuously fed to the fermenter.
● Side products are: 6-hydroxy-simvastatin, 3-hydroxy-iso-simvastatin and 3-desmethyl-3-carboxy-simvastatin:
O
HO
O
O
O
O
O
H H H
1
1 = simvastatin
2 = 6-β-hydroxy-simvastatin
3 = 6-β-hydroxy-methyl-simvastatin
Fig. 1.14.14.1 – 2
O
HO
H
HO
2
O
O
OH
O
HO
2
OH
O
O
HO
O
3
O
O
243