The enzyme Thermoanaerobacter brockii secondary alcohol dehydrogenase (TbSADH) has been identified as a good candidate for biocatalytic applications due to its wide substrate scope, thermostability and its ability to tolerate organic solvents. TbSADH reversibly catalyses the interconversion of ketones and secondary alcohols, displaying both high activity and high stereoselectivity. With the work presented here we assess whether density functional theory (DFT) and the quantum chemical cluster modelling approach can be used for elucidation of reaction mechanisms in NAD(P)- and metal ion dependent enzymes such as this. We have also investigated if the accuracy of the methods used is sufficient to reproduce, and thus potentially predict, experimentally determined enantioselectivities of metalloenzymes containing large cofactors, as has previously been shown for metal-free enzymes.1,2 Using an active site model of 300+ atoms the results are very encouraging and we are able to reproduce experimental results, including a reversal in enantioselectivity for acyclic alcohols that occurs upon extension of the carbon chain. 1. Lind, M. E. S.; Himo, F. Quantum Chemistry As a Tool in Asymmetric Biocatalysis: Limonene Epoxide Hydrolase Test Case. Angewandte Chemie Angew. Chem. 2013, 4661–4665. 2. Lind, M. E. S.; Himo, F. Theoretical Study Of Reaction Mechanism and Stereoselectivity of Arylmalonate Decarboxylase. ACS Catal. ACS Catalysis. 2014, 4153–4160.

Quantum chemical study of mechanism and stereoselectivity of zinc- and NADP-dependent secondary alcohol dehydrogenase

251st National Meeting (2016)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.