Biocatalysis has emerged as one of the most promising technologies to enable green synthesis of important chemicals, due to the ambient conditions generally applied for these reactions. Nonetheless, a general uptake of enzymatic transformations has been hindered by the perceived high cost of recombinant proteins. Recent interest in continuous flow from the synthetic chemistry community has now begun to spread to biotransformations, with protein immobilization playing a key part. As a consequence, continuous biotransformations using immobilized enzymes are becoming more accessible to nonexperts. This review will discuss several recent examples of continuous biotransformations that use immobilization, with a focus on examples involving fine chemical synthesis. It will also examine some of the issues that the community has as a whole, most importantly a lack of unified reporting tools to allow comparison and assessment of the different techniques.

We report a simple, mild, and synthetically clean approach to accelerate the rate of enzymatic oxidation reactions by a factor of up to 100 when compared to conventional batch gas/liquid systems. Biocatalytic decomposition of H O is used to produce a soluble source of O directly in reaction media, thereby enabling the concentration of aqueous O to be increased beyond equilibrium solubility under safe and practical conditions. To best exploit this method, a novel flow reactor was developed to maximize productivity (g product L h ). This scalable benchtop method provides a distinct advantage over conventional bio-oxidation in that no pressurized gas or specialist equipment is employed. The method is general across different oxidase enzymes and compatible with a variety of functional groups. These results culminate in record space-time yields for bio-oxidation.

Chiral vicinal amino alcohols are an important motif found in many biologically active molecules. In this study, biocatalytic reductive amination of α-hydroxy ketones with ammonia was investigated using engineered amine dehydrogenases (AmDHs) derived from the leucine amino acid dehydrogenase (AADH) from Lysinibacillus fusiformis. The AmDHs thus identified enabled the synthesis of (S)-configured vicinal amino alcohols from the corresponding α-hydroxy ketones in up to 99% conversions and >99% ee. One of the AmDH variants was used to prepare a key intermediate for the antituberculosis pharmaceutical ethambutol.

Fungal reductive aminases as effective biocatalysts for the preparation of chiral primary amines.