Biocatalytic Optical Resolution of DL-Pantolactone on an Industrial Scale
Sakayu SHIMIZU*, Tadanori MORIKAWA†, Kazumasa NITTA†, Keiji SAKAMOTO† and Koich WADA†
Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University; Kyoto-shi 606-8502 Japan
† Fuji Chemical Industries; Takaoka-shi 933-8511 Japan
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%; CO2, −30%; BOD, −62%; compared with the former chemical resolution method).
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