Thiamine diphosphate dependent enzymes are excellent catalysts for the asymmetric synthesis of the α-hydroxyketone (acyloin) structural motif, which is found in many pharmaceuticals and fine chemicals. In chapter 2, variants of transketolase from Saccharomyces cerevisiae were screened for the conversion of aliphatic aldehydes with hydroxypyruvate as donor substrate. The formation of a new hydrogen bond network was observed in the most successful variant D477E, which allowed for the accommodation of hydrophobic aldehydes within the enzyme’s polar active site. Decarboxylation of hydroxypyruvate was shown to render the carboligation reaction kinetically controlled, correcting the preceding notion of an irreversible conversion of substrates in literature.
|Qualification||Doctor of Philosophy|
|Award date||23 Apr 2021|
|Publication status||Published - 2021|
- kinetic control
- thiamine diphosphate