We succeeded in introducing an enzymatic step for the production of
D-pantolactone (
D-PL), a chiral building block for the commercial production of a vitamin,
D-pantothenic acid. The process involves stereoselective hydrolysis step with a novel fungal enzyme “lactonohydolase” as the catalyst for the resolution of
DL-PL. The enzyme isolated from
Fusarium oxysporum specifically hydrolyzes
D-PL to
D-pantoic acid (
D-PA); thus
DL-PL is easily separated into
D-PA and
L-PL.
When 700 g/L aqueous solution of
DL-PL was incubated with the fungal mycelia as the catalyst,
D-PL in the racemic mixture was almost completely hydrolyzed to
D-PA (96%ee). The mycelia were immobilized into calcium alginate gels for the practical purpose. When the gels were incubated in 350 g/L aqueous solution of
DL-PL for 21 h at 30 °C with automatic pH control (pH 7.3), 80–100% of the
D-PL was hydrolyzed. The resultant
D-PA in the reaction mixture had a high optical purity (93–98%ee) and the
L-PL remaining was unmodified. After 180 reaction cycles (i.e., 180 days), the gels retained about 60% of their initial activity.
Based on these results, we started the commercial production of
D-PL since 1999, through which it has been shown that the present process is highly satisfactory not only in economic aspect but also in environmental one (water, −49%; CO
2, −30%; BOD, −62%; compared with the former chemical resolution method).
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