Advances in the Enzymatic Reduction of Ketones

Abstract

Historically, biocatalytic ketone reductions involved the use of Baker's yeast. Within the last five years, a significant and growing number of isolated ketoreductases have become available that have rendered yeast-based reductions obsolete. The broad substrate range and exquisite selectivities of these enzymes repeatedly outperform other ketone reduction chemistries, making biocatalysis the general method of choice for ketone reductions. Presented here is a summary of our understanding of the capabilities and limitations of these enzymes.

Renewable Hydrogen Carrier — Carbohydrate: Constructing the Carbon-Neutral Carbohydrate Economy

“…The highest turn-over number (TTN) value for NAD recycling reported in the literature is >1,000,000 [86]. The pharmaceutical industry nearly stops further efforts in increasing TTN values of ~10,000-100,000 [87,88] due to high selling values of chiral compounds plus the additional regulatory requirements if the current process is modified. But it is vital that TTN values of NAD should be higher than 10 6 for the economically viable production of biocommodities [31].…”

Bioreductive production of enantiopure (S)-duloxetine intermediates catalyzed with ketoreductase ChKRED15

“…The bioreduction serves as a powerful approach for the production of optically active alcohols, which are widely used as fundamental intermediates for pharmaceuticals, agrochemicals and other products with chiral centers [1][2][3][4][5][6]. With the increased availability of recombinant ketoreductases, industrial-scale processes using cell-free enzymes coupled with efficient recycling systems have been developed rapidly in the past decade, which provides high volumetric productivity, excellent stereoselectivity, absence of side reactions and other economic advantages [7][8][9][10][11][12].…”

Rapid asymmetric reduction of ethyl 4-chloro-3-oxobutanoate using a thermostabilized mutant of ketoreductase ChKRED20

“…The reaction is generally catalyzed with microorganisms producing carbonyl reductases (or ketone reductases, KRED) or recombinant enzymes coupled with a proper cofactor regeneration system (Bornscheuer et al 2012;Hollmann et al 2011;Huisman et al 2010;Moore et al 2007;Ni and Xu 2012;Patel 2008). The recombinant enzymes are particularly preferred in recent industrial-scale setups for easy scale-up with high volumetric productivity, as well as the absence of side reactions (Goldberg et al 2007;Huisman et al 2010).…”