Biocatalysis for pharmaceutical intermediates: the future is now.

Biocatalysis is continuing to gain momentum and is now becoming a key component in the toolbox of the process chemist, with a place alongside chemocatalysis and chromatographic separations. The pharmaceutical industry demands a speed of development that must be on a parallel with conventional chemistry and high optical purity for complex compounds with multiple chiral centres. This review describes how these demands are being addressed to make biocatalysis successful, particularly by the use of micro-scale technology for high-speed catalyst screening and process development alongside discipline integration of biology and engineering with chemistry. Developments in recombinant technology will further expand the repertoire of biocatalysis in the coming years to new chemistries and enable catalyst design to fit the process. Further development of biocatalysis for green chemistry and high productivity processes can also be expected.

Substrate supply for effective biocatalysis.

Using biocatalysis for some chemical synthesis steps has unique advantages such as achieving higher product selectivity under ambient process conditions. However, a common limitation with such systems is the inhibition or toxicity posed by the starting substrate as well as limited aqueous solubility in many cases. In this review, we discuss the supply of substrate to bioconversions. The delivery of substrate via an auxiliary, which may be water-miscible, or a second phase such as a water-immiscible organic solvent, adsorbing resin, or a gas, is examined through recent examples in the field. Finally, guidelines for experimental planning and process considerations are suggested to facilitate the choice of substrate delivery method and accelerate process development.

Advances in the enzymatic reduction of ketones.

Historically, biocatalytic ketone reductions involved the use of Baker's yeast. Within the last five years, a significant and growing number of isolated ketoreductases have become available that have rendered yeast-based reductions obsolete. The broad substrate range and exquisite selectivities of these enzymes repeatedly outperform other ketone reduction chemistries, making biocatalysis the general method of choice for ketone reductions. Presented here is a summary of our understanding of the capabilities and limitations of these enzymes.