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.
References
May 1, 1989·Journal of Bacteriology·B González, R Vicuña
Jan 1, 1988·Archives of Microbiology·B GonzálezR Vicuña
Jul 26, 1988·Biochemistry·L J ReynoldsG L Kenyon
Mar 22, 1988·Biochemistry·P M WeissP F Cook
Jul 29, 1965·Biochimica Et Biophysica Acta·M J Selwyn
Jun 7, 2000·Chemistry : a European Journal·H IdingM Pohl
Jun 1, 2001·Methods : a Companion to Methods in Enzymology·R G Duggleby
Jun 1, 2001·Methods : a Companion to Methods in Enzymology·A Cornish-Bowden
Oct 10, 2002·Journal of the American Chemical Society·Pascal DünkelmannMichael Müller
Nov 15, 2002·Chemistry : a European Journal·Martina PohlMichael Müller
May 9, 2003·Natural Product Reports·Frank Jordan
Jan 8, 1963·Biochimica Et Biophysica Acta·W W CLELAND
Apr 7, 2005·Current Opinion in Chemical Biology·Kurt Faber, Wolfgang Kroutil
Jul 27, 2005·Biochemical Society Transactions·F J LeeperM D H Wood
Nov 24, 2005·The FEBS Journal·Tanja G MosbacherGeorg E Schulz
Oct 10, 2006·Biotechnology and Bioengineering·Falk HildebrandStephan Lütz
Oct 20, 2006·Chembiochem : a European Journal of Chemical Biology·Michael KnollMartina Pohl
Nov 3, 2006·Bioorganic Chemistry·Elena JanzenMartina Pohl
Nov 5, 1996·Biotechnology and Bioengineering·A J Straathof, J J Heijnen
Citations
Jun 22, 2011·Applied Microbiology and Biotechnology·Durda Vasić-RačkiAna Vrsalović Presečki
Mar 1, 2011·Current Opinion in Biotechnology·Wolfgang Wiechert, Stephan Noack
Dec 25, 2010·Biotechnology Journal·Gernot JägerJochen Büchs
Oct 30, 2016·Biotechnology Progress·Jan-Hendrik GroschAntje C Spieß
Oct 4, 2016·Biotechnology and Bioengineering·M N Cruz BournazouP Neubauer
Jun 10, 2018·Biotechnology Progress·Rüdiger OhsAntje C Spiess
Jun 18, 2019·Biotechnology Progress·Rüdiger OhsAntje C Spiess
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
Jul 8, 2021·Biotechnology and Bioengineering·Alexander SiggBernd Nidetzky
Mar 23, 2011·Chemical Reviews·Margarita BrovettoGustavo A Seoane
Jul 28, 2018·ACS Synthetic Biology·Vera D JägerUlrich Krauss