2.3 Pantothenic Acid and
Coenzyme A
About 6,000 t of calcium D-pantothenate are
produced annually. It is mainly used as an animal feed additive (80%). It is also used for
pharmaceutical, health care and food products. D-Pantothenyl alcohol (1,000 t aP1) is also
used for the same purposes. The commercial
production process involves reactions yielding
racemic pantolactone from isobutyraldehyde,
formaldehyde, and cyanide, optical resolution
of the racemic pantolactone to D-pantolactone, and condensation of D-pantolactone with
-alanine to form D-pantothenic acid. 3-Aminopropanol is used for D-pantothenyl alcohol
[major producers, Hoffmann-La Roche, Fuji
(Japan), and BASF]. The conventional optical
resolution which requires expensive alkaloids
as resolving agents is troublesome. Recently,
an efficient enzymatic method has been introduced into this optical resolution step (SHIMIZU et al., 1997). This enzymatic resolution uses
a novel fungal enzyme, lactonohydrolase, as
the catalyst. The enzyme catalyzes stereospecific hydrolysis of various kinds of lactones.
D-Pantolactone is a favorable substrate of this
enzyme, but the L-enantiomer is not hydrolyzed
Fig. 3. In situ NAD(P)H regeneration with glucose dehydrogenase (GDH) for the stereospecific reduction
of prochiral carbonyl compounds to chiral alcohols.
at all (SHIMIZU et al., 1992). Thus, the racemic
mixture can be separated into D-pantoic acid
and L-pantolactone (Fig. 4). As this lactonase
reaction is an intermolecular ester bond hydrolysis, the pantolactone as the substrate
needs not to be modified for resolution, which
is one of the practical advantages of the use of
this enzyme. Several filamentous fungi of the
genera Fusarium, Gibberella, and Cylindrocarpon show high activity of this enzyme