Mechanistic kinetic model for symmetric carboligations using benzaldehyde lyase

Biotechnology and Bioengineering
Michael ZavrelA Spiess

Abstract

For reactions using thiamine diphosphate (ThDP)-dependent enzymes many empirically-derived kinetic models exist. However, there is a lack of mechanistic kinetic models. This is especially true for the synthesis of symmetric 2-hydroxy ketones from two identical aldehydes, with one substrate acting as the donor and the other as the acceptor. In this contribution, a systematic approach for deriving such a kinetic model for thiamine diphosphate (ThDP)-dependent enzymes is presented. The derived mechanistic kinetic model takes this donor-acceptor principle into account by containing two K(m)-values even for identical substrate molecules. As example the stereoselective carbon-carbon coupling of two 3,5-dimethoxy-benzaldehyde molecules to (R)-3,3',5,5'-tetramethoxy-benzoin using benzaldehyde lyase (EC 4.1.2.38) from Pseudomonas fluorescens is studied. The model is derived using a model-based experimental analysis method which includes parameter estimation, model analysis, optimal experimental design, in silico experiments, sensitivity analysis and model revision. It is shown that this approach leads to a robust kinetic model with accurate parameter estimates and an excellent prediction capability.

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Citations

Jun 22, 2011·Applied Microbiology and Biotechnology·Durda Vasić-RačkiAna Vrsalović Presečki
Mar 1, 2011·Current Opinion in Biotechnology·Wolfgang Wiechert, Stephan Noack
Oct 30, 2016·Biotechnology Progress·Jan-Hendrik GroschAntje C Spieß
Oct 4, 2016·Biotechnology and Bioengineering·M N Cruz BournazouP Neubauer
Nov 3, 2016·Chembiochem : a European Journal of Chemical Biology·Patrick C F BuchholzJürgen Pleiss
Jul 13, 2018·Biotechnology Journal·Patrick C F BuchholzJürgen Pleiss
Mar 23, 2011·Chemical Reviews·Margarita BrovettoGustavo A Seoane

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