Ketopantoyl lactone reduction

Reduction of ketopantoic acid to D-pantoic acid (0, (4) in Fig. 8). Agrobacterium sp. S-246 is a good source of ketopantoic acid reductase. The yield of D-pantoic acid reached 119 g/1 (molar yield, 90% optical purity, 98% e.e.) on incubation with washed cells of the bacterium [102]. From a practical point of view, ketopantoic acid reduction with Agrobacterium cells has several advantages over ketopantoyl lactone reduction with Candida (or Rhodotorula) cells. The former results in a higher product yield, molar conversion and optical purity of the product than the latter. It is necessary to maintain the substrate level at lower than 3% in the case of the ketopantolactone reduction, but not for the ketopantoic acid reduction. 

Figure 19.1. Diversity of microbial reduction of ketopantoyl lactone (a) and COBE (b). A, yeasts O, molds , bacteria , actinomycetes , basidiomycetes PL, pantoyl lactone KPL, ketopantoyl lactone.

Shimizu, S., Hata, H., and Yamada H. 1984. Reduction of ketopantoyl lactone to D-(-)-pantoyl lactone by microorganisms. Agric. Biol. Chem., 48,2285-2291. 

Asymmetric reduction of ketopantoyl lactone is an effective biomimetic route to R-(- )-pantolactone, an intermediate in the synthesis of the important d-( + )-pantothenic acid (a component of vitamins B and of coenzyme A) ... 

Cyclodextrin has also been used to control the enantioselectivity of bioreductions1119-1211. When added to a reaction mixture, the substrate can reside in the cyclodextrin, which decreases the effective substrate concentration around the enzyme and results in the domination of reactions involving enzymes with low KM. The effect can be demonstrated by the reduction of ketopantoyl lactone by yeast. The enantioselectivity was improved from 73% to 93% by adding p-cyclodextrin to the reaction mixture. The improvement in enantioselectivity of the reduction in the presence of enzymes with different enantioselectivities and Km values by decreasing the substrate concentration was confirmed by the ineffectiveness of a-cyclodextrin which is too small to include the substrate. It was also confirmed by dilution of the reaction mixture, which improved the enantioselectivity in the absence of cyclodextrin. 

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