Biocatalytical production of (5S)-hydroxy-2-hexanone.
Biocatalytical approaches have been investigated in order to improve accessibility of the bifunctional chiral building block (5S)-hydroxy-2-hexanone ((S)-2). As a result, a new synthetic route starting from 2,5-hexanedione (1) was developed for (S)-2, which is produced with high enantioselectivity (ee >99%). Since (S)-2 can be reduced further to furnish (2S,5S)-hexanediol ((2S,5S)-3), chemoselectivity is a major issue. Among the tested biocatalysts the whole-cell system S. cerevisiae L13 surpasses the bacterial dehydrogenase ADH-T in terms of chemoselectivity. The use of whole-cells of S. cerevisiae L13 affords (S)-2 from prochiral 1 with 85% yield, which is 21% more than the value obtained with ADH-T. This is due to the different reaction rates of monoreduction (1-->2) and consecutive reduction (2-->3) of the respective biocatalysts. In order to optimise the performance of the whole-cell-bioreduction 1 2 with S. cerevisiae, the system was studied in detail, revealing interactions between cell-physiology and xenobiotic substrate and by-products, respectively. This study compares the whole-cell biocatalytic route with the enzymatic route to enantiopure (S)-2 and investigates factors determining performance and outcome of the bioreductions.
Katzberg
Michael
M
Institute of Biochemistry, Dresden University of Technology, Dresden, D-01062, Dresden, Germany.
Wechler
Kerstin
K
Müller
Marion
M
Dünkelmann
Pascal
P
Stohrer
Jürgen
J
Hummel
Werner
W
Bertau
Martin
M
D000426:Alcohol Dehydrogenase / Q000378:metabolism; D055162:Biocatalysis; D002384:Catalysis; D006588:Hexanones / Q000737:chemistry* / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000378:metabolism; D046968:Thermoanaerobacter / Q000378:metabolism
D006588:Hexanones; D000426:Alcohol Dehydrogenase; C535060:5-hydroxy-2-hexanone