From Wikipedia,
the free encyclopedia.
Biocatalysis can be
defined as the utilization of
natural
catalysts, called
enzymes, to perform chemical
transformations on
organic compounds. Both
enzymes that have been more or
less isolated or enzymes still
residing inside living cells are
emloyed for this task.
History
Biocatalysis underpins some of
the oldest chemical
transformations known to humans,
for
brewing predates recorded
history. The oldest records of
brewing are about 6000 years old
and refer to the
Sumerians.
The employment of enzymes and
whole cells have been important
for many industries for centuries.
The most obvious usages have been
in the food and drink businesses
where the production of wine,
beer, cheese etc. is dependent on
the effects of the
microorganisms.
More than one hundred years
ago, biocatalysis was employed to
do chemical transformations on
non-natural man-made
organic compounds, and the
last 30 years have seen a
substantial increase in the
application of biocatalysis to
produce
fine chemicals, especially for
the
pharmaceutical industry.
Advantages of Biocatalysis
The key word for
organic synthesis is
selectivity which is necessary
to obtain a high yield of a
specific product. There are a
large range of selective
organic reactions available
for most synthetic needs. However,
there is still one area where
organic chemists are struggling,
and that is when
chirality is involved,
although considerable progress in
chiral synthesis has been
achieved in recent years.
Enzymes display three major types
of selectivities:
Chemoselectivity
Since the purpose of an enzyme is
to act on a single type of
functional group, other sensitive
functionalities, which would
normally react to a certain extent
under chemical catalysis, survive.
As a result, biocatalytic
reactions tend to be "cleaner" and
laborous purification of product(s)
from impurities emerging through
side-reactions can largely be
omitted.
Regioselectivity and
Diastereoselectivity
Due to their complex
three-dimensional structure,
enzymes may distinguish between
functional groups which are
chemically situated in different
regions of the substrate molecule.
Enantioselectivity
Since almosost all enzymes are
made from L-amino acids, enzymes
are chiral catalysts. As a
consequence, any type of chirality
present in the substrate molecule
is "recognized" upon the formation
of the enzyme-substrate complex.
Thus a prochiral substrate may be
transformed into an optically
active product and both
enantiomers of a racemic substrate
may react at different rates.
These reasons, and especially the
latter, are the major reasons why
synthetic chemists have become
interested in biocatalysis. This
interest in turn is mainly due to
the need to synthesise
enantiopure compounds as
chiral building blocks for
drugs and
agrochemicals.
Another important advantage of
biocatalysts are that they are
environmentally acceptable, being
completely degraded in the
environment. Furthermore the
enzymes act under mild conditions,
which minimizes problems of
undesired side-reactions such as
decomposition,
isomerization,
racemization and
rearrangement, which often
plague traditional methodology.
Chiral building blocks from
biocatalysis
The use of Biocatalysis to
obtain enantiopure compounds can
be divided into two different
methods;
1. Kinetic resolution of a
racemic mixture
2. Biocatalysed asymmetric
synthesis
In kinetic resolution of a
racemic mixture, the presence
of a chiral object (the enzyme)
converts one of the enantiomers
into product at a greater rate
than the other enantiomer.
The racemic mixture has now been
transformed into a mixture of two
different compounds, making them
separable by normal methodology.
The maximum yield in such kinetic
resolutions is 50%, since a yield
of more than 50% means that some
of wrong isomer also has reacted,
giving a lower
enantimeric excess. Such
reactions must therefore be
terminated before equilibrium is
reached. If it is possible to
perform such resolutions under
conditions where the two
substrate- enantiomers are
racemizing continously, all
substrate may in theory be
converted into enantiopure
product. This is called dynamic
resolution.
In biocatalysed asymmetric
synthesis, a non-chiral unit
becomes chiral in such a way that
the different possible
stereoismers are formed in
different quantities. The
chirality is introduced into the
substrate by influence of enzyme,
which is chiral.
References
- Anthonsen, T. Reactions
Catalyzed by Enzymes. In
Applied Biocatalysis, 2.
Ed. ; Adlercreutz. P.; Straathof,
A. J. J. Eds.; Harwood Academic
Publishers: UK, 1999; pp
18-53
- Faber, K.
Biotransformations in Organic
Chemistry, 4th ed.,
Springer-Verlag, Berlin 2000.
- Jayasinghe L. Y., Smallridge
A. J., and Trewhella M. A.;
Tetrahedron Letters, 1993,
3949.
