natural cofactors, which cannot be replaced by more economical man-made chemical substitutes.
Some cofactors are rather sensitive molecules and are gradually destroyed due to
undesired side reactions occurring in the medium, in particular NAD(P)H and ATP.
Cofactors are too expensive to be used in the stoichiometric amounts formally
required. Accordingly, when coenzyme-dependent enzymes are employed, the
corresponding coenzymes are used in catalytic amounts in conjunction with an
efficient and inexpensive in-situ regeneration system. Some cofactor recycling
methods are highly developed and are applicable to industrial scale, others are
still problematic (Table 1.6). Fortunately, some coenzymes are tightly bound to
their respective enzymes so that external recycling is not required. Whereas the
redox potential of NADH and NADPH is largely independent of the type of
enzyme, the potential of flavin cofactors is significantly determined by the protein,
to which it is (covalently or noncovalently) attached. Consequently, the redox
capabilities of flavoproteins encompass a broader range of reactions compared to
nicotinamide-depending enzymes.
Many enzymes require coordinated metals such as (Lewis-acid type) Zn, Ca, Mg
or redox-active Fe, Cu, Mn. Ni, Co, V, W and Mo are less common. In most cases,
metals are tightly bound to the enzyme and are not an issue if they are supplied to
the medium.
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Table 1.6 Common coenzymes required for biotransformations
Coenzyme
Reaction type
Recycling
a
NAD
+ /NADH
Carbonyl reduction &
(+) [+++]
NADP
+ /NADPH
Alcohol oxidation
(+) [++]
ATP
b
Phosphorylation
(+) [+]
SAM
C 1 -alkylation
(+) [Æ]
Acetyl-CoA
C 2 -alkylation
(+) [Æ]
Flavins
Baeyer-Villiger-, N- & S-oxidation, C¼C reduction
(À)
c
Pyridoxal-phosphate
Transamination, racemization
(À)
Thiamine diphosphate
C–C ligation
(À)
Metal-porphyrins
Peroxidation, oxygenation
(À)
c
Biotin
Carboxylation
(À)
a
Recycling of a cofactor is necessary (+) or not required (À), the feasibility of which is indicated in
square brackets ranging from ‘simple’ [+++] to ‘complicated’ [Æ]
b
For other triphosphates, such as GTP, CTP, and UTP, the situation is similar
c
Many flavin- and metal porphyrin-dependent mono- or dioxygenases require additional
NAD(P)H as an indirect reducing agent
24
1 Introduction and Background Information
Some cofactors are rather sensitive molecules and are gradually destroyed due to
undesired side reactions occurring in the medium, in particular NAD(P)H and ATP.
Cofactors are too expensive to be used in the stoichiometric amounts formally
required. Accordingly, when coenzyme-dependent enzymes are employed, the
corresponding coenzymes are used in catalytic amounts in conjunction with an
efficient and inexpensive in-situ regeneration system. Some cofactor recycling
methods are highly developed and are applicable to industrial scale, others are
still problematic (Table 1.6). Fortunately, some coenzymes are tightly bound to
their respective enzymes so that external recycling is not required. Whereas the
redox potential of NADH and NADPH is largely independent of the type of
enzyme, the potential of flavin cofactors is significantly determined by the protein,
to which it is (covalently or noncovalently) attached. Consequently, the redox
capabilities of flavoproteins encompass a broader range of reactions compared to
nicotinamide-depending enzymes.
Many enzymes require coordinated metals such as (Lewis-acid type) Zn, Ca, Mg
or redox-active Fe, Cu, Mn. Ni, Co, V, W and Mo are less common. In most cases,
metals are tightly bound to the enzyme and are not an issue if they are supplied to
the medium.
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Table 1.6 Common coenzymes required for biotransformations
Coenzyme
Reaction type
Recycling
a
NAD
+ /NADH
Carbonyl reduction &
(+) [+++]
NADP
+ /NADPH
Alcohol oxidation
(+) [++]
ATP
b
Phosphorylation
(+) [+]
SAM
C 1 -alkylation
(+) [Æ]
Acetyl-CoA
C 2 -alkylation
(+) [Æ]
Flavins
Baeyer-Villiger-, N- & S-oxidation, C¼C reduction
(À)
c
Pyridoxal-phosphate
Transamination, racemization
(À)
Thiamine diphosphate
C–C ligation
(À)
Metal-porphyrins
Peroxidation, oxygenation
(À)
c
Biotin
Carboxylation
(À)
a
Recycling of a cofactor is necessary (+) or not required (À), the feasibility of which is indicated in
square brackets ranging from ‘simple’ [+++] to ‘complicated’ [Æ]
b
For other triphosphates, such as GTP, CTP, and UTP, the situation is similar
c
Many flavin- and metal porphyrin-dependent mono- or dioxygenases require additional
NAD(P)H as an indirect reducing agent
24
1 Introduction and Background Information