Rio Yamanaka

Recent developments in asymmetric reduction of ketones with biocatalysts

Herein we review recent advances in the asymmetric reduction of ketones by biocatalysts. Included are discussions on recent developments in methodologies to control enantioselectivities of catalytic reactions, and examples of practical applications that reduce various types of ketones are also shown.

Cyanobacterium-catalyzed asymmetric reduction of ketones

Abstract Synechococcus sp. PCC 7942, a cyanobacterium, acted as a biocatalyst to reduce aryl methyl ketones into the corresponding ( S )-alcohols with excellent enantioselectivities under illumination.

Light-mediated regulation of asymmetric reduction of ketones by a cyanobacterium

The stereochemical course of the asymmetric reduction of ketones by a photosynthetic microbe is largely regulated by light. Thus, we find that the enantioselectivity of the reduction of α,α-difluoroacetophenone with Synechococcus elongatus PCC 7942 increases as a result of illumination with fluorescent light. Furthermore, DCMU, an inhibitor of photosynthesis, affects the stereoselectivity, and, under illumination decreases the enantioselectivity of the reduction.

Light mediated cofactor recycling system in biocatalytic asymmetric reduction of ketone

Reduction of an artificial ketone by Synechococcus elongatus PCC 7942 proceeds smoothly by the aid of light. The efficiency of the reaction is very high since the coenzyme NADPH is regenerated by using light energy.

Reduction of exogenous ketones depends upon NADPH generated photosynthetically in cells of the cyanobacterium Synechococcus PCC 7942

Effective utilization of photosynthetic microorganisms as potential biocatalysts is favorable for the production of useful biomaterials and the reduction of atmospheric CO2. For example, biocatalytic transformations are used in the synthesis of optically active alcohols. We previously found that ketone reduction in cells of the cyanobacterium Synechococcus PCC 7942 is highly enantioselective and remarkably enhanced under light illumination. In this study, the mechanism of light-enhanced ketone reduction was investigated in detail using several inhibitors of photosynthetic electron transport and of enzymes of the Calvin cycle. It is demonstrated that light intensity and photosynthesis inhibitors significantly affect the ketone reduction activity in Synechococcus. This indicates that the reduction correlates well with photosynthetic activity. Moreover, ketone reduction in Synechococcus specifically depends upon NADPH and not NADH. These results also suggest that cyanobacteria have the potential to be utilized as biocatalytic systems for direct usage of light energy in various applications such as syntheses of useful compounds and remediation of environmental pollutants.

Chapter 3 – Photobiocatalysis

Optically active alcohols are useful for organic syntheses of chemical catalysts, liquid crystals, flavors, agrochemicals, and drugs. To synthesize optically active alcohols, chemical and biological catalysts have been used and most of the reports on biocatalytic transformations have been focused on heterotrophic microorganisms. In biocatalyzed reduction, enzymes such as dehydrogenases and reductases require chemical energy such as NAD(P)H to reduce a ketone to the corresponding alcohol. The oxidized form of the coenzyme which is generated by the reduction of a ketone is necessarily reduced to the reduced form in order to proceed with the reduction reaction. In the heterotrophic microorganism-catalyzed reduction, hydrogen sources, such as sugars and alcohols, are used for the reduction of the oxidized form of the coenzyme. Sugars are originally produced by photosynthesis with phototroph (photosynthetic organisms) and alcohols are produced from sugars or a fossil fuel resource, which was produced by phototroph in the distant past. Thus the heterotrophic microorganism-catalyzed reduction system utilizes photosynthesis indirectly. On the other hand, photoautotrophic biocatalysts can use light as an energy source not only for growing but also for asymmetric reduction directly; they are environmentally friendly catalysts: they absorb carbon dioxide and generate oxygen. In terms of energy acquisition efficiency, photoautotrophic organisms such as microalgae, plant-cultured cells, and germinated plants appear to be the most effective biocatalytic agents. We call photoautotrophic organisms “photobiocatalysts” when they are used as biocatalysts. In this chapter, reduction using photobiocatalysts is mainly introduced.