into Aspergillus oryzae [537]. A corresponding enantiocomplementary L-specific
lactonase was identified in Agrobacterium tumefaciens [538].
More recently, lactonases were employed in the biodegradation of mycotoxins,
e.g. zearalenone [539]. Several lactonases were shown to possess also promiscuous
phosphotriesterase-activities, which makes them valuable in the bioremediation of
neurotoxic organophosphorus agents, which were widely employed as chemical
warfare agents and as pesticides, such as parathion [540, 541].
2.1.4 Hydrolysis and Formation of Phosphate Esters
The hydrolysis of phosphate esters can be equally achieved by chemical methods
and by phosphate ester hydrolases (phosphatases) and the application of enzymes
for this reaction is only advantageous if the substrate is susceptible to decomposition. Thus, the enzymatic hydrolysis of phosphates has found only a limited number
of applications. The same is true concerning the enantioselective hydrolyses of
racemic phosphates affording a kinetic resolution.
In contrast, the formation of phosphate esters is of importance, particularly when
regio- or enantioselective phosphorylation is required. On the one hand, numerous
bioactive agents display their highest activity only when phosphorylated, for instance
the hallucinogen psilocibin found in ‘magic mushrooms’. On the other hand, phosphorylation is a common strategy to increase the solubility of orally administered
drugs [542, 543]. For instance, prednisolone phosphate is a water-soluble prodrug
used as immunosuppressant and the non-natural nucleoside phosphate fludarabin is
employed as cytostatic for the treatment of leukemia (Scheme 2.71).
OH
O
O
OH
O
O
CO 2 H
OH
HO
CO 2 H
N
H
O
OH
HO
DL
Fusarium oxysporum
lactonase
buffer pH 7
L
+
e.e. 96%
ex-situ racemisation ΔT
D-pantothenic acid (vitamin B5)
steps
E = 35
D
Scheme 2.70 Resolution of pantolactone using a lactonase
N
H
O
NMe 2
P
P
Psilocibin
O
H
H
H
HO
HO
O
O
P
Prednisolone phosphate
O
OH
HO
N
N
N
N
F
NH 2
O
Fludarabin
Scheme 2.71 Phosphorylated bioactive compounds
104
2 Biocatalytic Applications
lactonase was identified in Agrobacterium tumefaciens [538].
More recently, lactonases were employed in the biodegradation of mycotoxins,
e.g. zearalenone [539]. Several lactonases were shown to possess also promiscuous
phosphotriesterase-activities, which makes them valuable in the bioremediation of
neurotoxic organophosphorus agents, which were widely employed as chemical
warfare agents and as pesticides, such as parathion [540, 541].
2.1.4 Hydrolysis and Formation of Phosphate Esters
The hydrolysis of phosphate esters can be equally achieved by chemical methods
and by phosphate ester hydrolases (phosphatases) and the application of enzymes
for this reaction is only advantageous if the substrate is susceptible to decomposition. Thus, the enzymatic hydrolysis of phosphates has found only a limited number
of applications. The same is true concerning the enantioselective hydrolyses of
racemic phosphates affording a kinetic resolution.
In contrast, the formation of phosphate esters is of importance, particularly when
regio- or enantioselective phosphorylation is required. On the one hand, numerous
bioactive agents display their highest activity only when phosphorylated, for instance
the hallucinogen psilocibin found in ‘magic mushrooms’. On the other hand, phosphorylation is a common strategy to increase the solubility of orally administered
drugs [542, 543]. For instance, prednisolone phosphate is a water-soluble prodrug
used as immunosuppressant and the non-natural nucleoside phosphate fludarabin is
employed as cytostatic for the treatment of leukemia (Scheme 2.71).
OH
O
O
OH
O
O
CO 2 H
OH
HO
CO 2 H
N
H
O
OH
HO
DL
Fusarium oxysporum
lactonase
buffer pH 7
L
+
e.e. 96%
ex-situ racemisation ΔT
D-pantothenic acid (vitamin B5)
steps
E = 35
D
Scheme 2.70 Resolution of pantolactone using a lactonase
N
H
O
NMe 2
P
P
Psilocibin
O
H
H
H
HO
HO
O
O
P
Prednisolone phosphate
O
OH
HO
N
N
N
N
F
NH 2
O
Fludarabin
Scheme 2.71 Phosphorylated bioactive compounds
104
2 Biocatalytic Applications