Discovery, Evolution and Synthetic Applications of Phenylalanine Ammonia-Lyase

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Abstract

The emergence of biocatalysis and biotechnology in the pharmaceutical and fine chemical industry has transformed the way we manufacture high value chemicals. In an era of geo-political uncertainty, dwindling natural resources and political pressure to combat climate change, the wider chemical industry has invested in biocatalysis where it has played a vital role in developing sustainable manufacturing processes. Other factors such as regulatory hurdles, driving down costs, societal forces, where consumers are demanding products produced from natural sources has played a key role in the evolution of this field. Perhaps the biggest influence came from the scientific community, with decreasing cost of gene synthesis and sequencing (a bottleneck for many years in this field) following Moore̢۪s law has expedited development in this area of research and has led to several commercial applications in the pharmaceutical and fine chemical industry. The purpose of this thesis is to highlight the synthetic application of Phenylalanine Ammonia-Lyase and its potential in the sustainable manufacturing of amino acid API̢۪s. This report will cover extensively the background of this enzyme, its uses in chemoenzymatic processes and in synthetic biology followed by recent work on expanding the substrate scope through enzyme discovery, evolution and synthetic biochemistry.

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