Discovery, characterisation and synthetic application of Omega-transaminases

UoM administered thesis: Phd

  • Authors:
  • Jin Xu

Abstract

Omega-Transaminases are a class of PLP-dependent enzymes which catalyse the reversible transamination reaction between carbonyl compounds and amine donors. Previously, Omega-transaminases have been widely applied in the production of chiral amines. The expansion of the substrate scope towards Omega-transaminases provides the potential to exploit new biocatalytic synthetic routes involving regioselective amination. Among the initial comparison of Omega-transaminases from different species, a wild-type Omega-transaminase from Bacillus megaterium was identified to possess high activity. A characterisation system was developed for screening activity of substrates towards both amine and carbonyl substrates towards BM-TA. Meanwhile, an (S)-aminotetralin based assay was developed to meet the requirement of screening aromatic carbonyl compounds. Several dicarbonyl compounds were determined to be accepted by BM-TA, which were subsequently applied in the synthesis of N-heteroaromatic compounds. Afterwards, two Omega-transaminase mediated biocatalytic approaches for the synthesis of substituted pyrazines and pyrroles were developed respectively and a self-sufficient amine donor applying a reversible amine functionality shuttle system was discovered.

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Original languageEnglish
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Award date1 Aug 2018