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Title: Developing biocatalysts for the reduction of carboxylic acids to aldehydes
Author: Hill, Andrew
Awarding Body: University of Manchester
Current Institution: University of Manchester
Date of Award: 2017
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The research presented in this thesis describes the characterisation and application of two carboxylic acid reductases (CAR) from the bacteria Mycobacterium marinum (MmCAR) and Nocardia iowensis (NiCAR), as biocatalysts for the chemoselective reduction of carboxylic acids to aldehydes. A broad substrate panel was screened against the enzymes, and the results presented herein with discussion reveal that the two enzymes have a number of similarities and differences. Although the two enzymes are not enantiocomplimentary, NiCAR has a high enantioselectivity towards some substrates tested, whereas MmCAR is less enantioselective. The broad nature of the substrate panel included compounds of industrial and pharmaceutical importance, as well as waste-stream compounds of biorefineries. A kinetics study has been performed on these MmCAR and the results are presented herein. The two enzymes have been demonstrated to be particularly well suited to whole-cell biocatalysis, producing aldehyde products in high yield and purity with a simple extractive workup. CARs have been coupled to two other enzymes (ω-transaminase and imine reductase) in order to produce chiral cyclic amines from achiral keto-carboxylic acids. These chiral cyclic amines are important motifs found in a wide range of pharmaceutical and bioactive natural products. Finally, the coupling of CARs and transaminase with a chromogenic substrate resulted in colonies expressing CAR activity to be visualised, allowing the principal of a novel colony-based, solid phase screen for CAR activity to be established.
Supervisor: Turner, Nicholas Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: biocatalysis ; carboxylic acid reductase ; reduction ; aldehydes ; bioreduction