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Title: Enantioselective decarboxylativeprotonation of malonic acids using aryl malonate decarboxylase
Author: Goodall, Mark John
Awarding Body: University of Manchester
Current Institution: University of Manchester
Date of Award: 2012
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Abstract:
The demand for new methods through which important enantiopure compounds can be produced is increasing within the chemical industry. In this regard, one group of interesting compounds are enantiopure carboxylic acids as traditional methods towards producing these compounds that rely on a process known as enantioselective decarboxylative protonation (EDP) are often insufficient due to a combination of factors including low yields, low enantioselectivities, the need for environmentally deleterious reaction conditions and high costs. Due to the shortcomings of these synthetic techniques, the application of biological systems is an alternative method that has come to the forefront of current research, which is because biological systems often boast a number of advantages over traditional chemical methods. Described within this thesis is one such biological method towards the production of enantiopure carboxylic acid compounds via EDP, a method that utilises the enzyme aryl malonate decarboxylase (AMDase). This research follows on from previous work detailing the mechanism this enzyme utilises toperform decarboxylation reactions and specifically looks into the substrate specificity that thisenzyme possesses. This work allows us to see how flexible this method is with regards to theproduction of a range of different carboxylic acid products, which is important as previous chemical methods are often limited by a lack of diversity. It also allows us to see how the kinetic parameters of the enzyme catalysed reactions change dependent on the identity of the substrate, allowing us to better justify the currently proposed mechanism and to better direct attempts to improve the enzyme through mutagenesis experiments. Indeed, several mutagenesis experiments have also been performed in an attempt to producevariants of the enzyme that would have either an increased enzyme scope or better reactivity with currently known substrates, and this work is also detailed within this thesis.
Supervisor: Micklefield, Jason Sponsor: BBSRC
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.564336  DOI: Not available
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