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Letters in Organic Chemistry

Editor-in-Chief

ISSN (Print): 1570-1786
ISSN (Online): 1875-6255

Letter Article

How Medium Affects the Activity and Stereopreference of Thermoanaerobacter ethanolicus Secondary Alcohol Dehydrogenase Catalyzed Reduction of Ketones

Author(s): Ibrahim Karume*, Simon Bbumba and Simon Tewolde

Volume 20, Issue 5, 2023

Published on: 07 December, 2022

Page: [395 - 400] Pages: 6

DOI: 10.2174/1570178620666221021103540

Price: $65

Abstract

The activity and selectivity of W110G Thermoanaerobacter ethanolicus secondary alcohol dehydrogenase were altered by cosubstrate and cosolvent at varying temperatures. A sharp drop in the enantiomeric excess (ee) was observed at 60°C in the first 3 h, suggesting increased selectivity mistakes in the reduction of 4-phenyl-2-butanone to the expected (S)-4-phenyl-2-butanol using 5% v/v of 2-propanol as a cosubstrate. The ee increased exponentially with cosubstrate concentration, reaching ≥94% with 30-70% v/v 2-propanol. However, a decrease in enzyme activity was noticed at ≥30% v/v 2-propanol by a sharp drop in conversion. The lowest ee (<3%) was registered using 5% v/v 2- propanol at 30-40°C, which prolonged enzyme life that allowed reversible redox reaction with selectivity mistakes to give the R-alcohol compared to ≥18% ee at 50-60°C, where faster reaction rates promoted selectivity mistake, but enzyme life was shortened by protein denaturation at the elevated temperatures. Water-miscible and immiscible organic cosolvents (25% v/v) increased enzyme selectivity. For methanol, ethanol, ethylene glycol and tert-butanol, the activity/conversion decreased with an increase in pKa and log P while the stereoselectivity/ee increased.

Keywords: Chiral compounds, organic cosolvents, hepatotoxicity, stereoselectivity, ketones, alcohol dehydrogenase.

Graphical Abstract
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