SYED T. AHMED, NICHOLAS J. WEISE, FABIO PARMEGGIANI, NICHOLAS J. TURNER*
*Corresponding author
Manchester Institute of Biotechnology, School of Chemistry, University of Manchester,
Manchester, United Kingdom

Abstract

Phenylalanine ammonia lyase has played a key role in the sustainable production of non-natural amino acids as chiral building blocks for pharmaceutical applications, as demonstrated, for instance, by the production of (S)-2-indolinecarboxylic acid by DSM. In recent years, the cyanobacterial PAL from Anabaena variabilis has been shown to be a robust enzyme in biocatalytic reactions in terms of stability and substrate scope. This mini-review highlights the work conducted in our group, particularly in the scale-up and intensification of the PAL reaction and its application towards the synthesis of novel, high value chiral intermediates through chemo-enzymatic processes.

INTRODUCTION

The concept of green chemistry has been around for more than five decades and it was only the latter part of the past century that witnessed the evolution of the field with the development of the 12 core “principles” of green chemistry (1).
These principles have been used to guide future efforts in developing green synthetic processes to lower costs and to reduce the carbon footprint.
With dwindling natural resources and political pressure to combat pollution and global warming, the pharmaceutical and fine chemicals industries have gradually begun to develop sustainable manufacturing processes. Other factors such as regulatory issues, business requirements (driving down costs), societal forces (consumers demanding products from natural sources or ‘green’ products) and scientific and technological advances (decreasing cost of DNA synthesis and sequencing following Moore’s Law) have played vital roles in the evolution of this field (2).

One such example is the use of enzymes for chemical synthesis, which has revolutionised the field of green chemistry. The advent of biotechnology has mitigated several proble ...