Bioreduction in Aqueous Systems

Water is a natural solvent of choice for biocatalysis. However, considering the rather hydrophobic nature of most substrate/product couples used, water seems a rather unsuitable solvent. From the ecotoxicity aspect, water can be easily contaminated by organic and metallic impurities from the reaction, and thus generally requires prior waste treatment before released into the environment 

Xu and coworkers reported several robust carbonyl reductases discovered via in silico data rnining approaches and developed a set of water-based bioreduction processes for efficient synthesis of functionalized optically active a- and P-hydroxy esters [2-4]. As shown in Table 9.1, several a- and P-keto esters were asymmetrically reduced at high loads using a carbonyl reductase mined from Candida abrata 

Substrate Substrate loading 1) Conversion (%) Isolated yield %) ee (%)  

It should be mentioned that the efficient reduction processes at extremely high substrate loading in aqueous media are achieved under the precondition of an available reductase with exceptionally high activity and substrate tolerance. Within these extraordinary cases, the hardly water-soluble substrate, in fact, serves as a second phase [5], as the solubility limit is exceeded. One problem associated with the large amount of substrate in aqueous media is the tendency to form emulsions in the workup, requiring tedious product separation and decrease in isolated yields. 

Administration of water-miscible organic solvents is a straightforward method to increase the solubility of hydrophobic reactants. A monophasic aqueous-organic system can considerably reduce the mass-transfer limitations, leading to more rapid reaction rates for hydrophobic compounds. 

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