Thermostable Thermoanaerobacter alcohol dehydrogenases and their use in organic synthesis

The thermo- and solvent-stable enzymes from extremophiles are an area of tremendous biotechnological potential, particularly in the context of “green” synthesis and achieving high stereoselectivity. The thermostable alcohol dehydrogenases (ADHs) from microorganisms within the genus of Thermoanaerobacter are noteworthy as they generate ethanol from glycolysis intermediates. Additionally, their secondary alcohol dehydrogenases (TSADHs) asymmetrically reduce ketones to their corresponding alcohols in organic solvent systems at a wide range of temperatures. Efforts to understand the thermostability of TSADHs relative to their mesophilic counterparts has revealed that relatively few changes in their structure are responsible for their improved stability. While the range of ketones that can be reduced is somewhat limited, efforts to engineer ADHs that can accommodate larger substrates and alter their selectivity using a combination of detailed structural models and rational design has resulted in improved TSADHs capable of the asymmetric reduction of larger ketones to their corresponding alcohols.