Reaction engineering analysis of hydroxyisobutyric acid production with recombinant microorganisms

Torben Höfel, doctoral thesis Technische Universität München, 2011

The microbial production of hydroxyisobutyric acid may become an option for the delivery of polymethylmethacrylate (acrylic glass) from renewable resources. For this purpose the microbial production of 2-hydroxyisobutyric acid from fructose with genetically engineered Cupriavidus necator was investigated in stirred tank bioreactors with respect to varying reaction conditions. For the first time it was shown that 2-hydroxyisobutyric acid can be produced by microbial fermentation in concentrations exceeding 7 g L-1. Further detailed reaction engineering studies of recombinant Escherichia coli were carried out for the production of succinic acid as an intermediate for microbial synthesis of 3-hydroxyisobutyric acid. With appropriate process conditions and additional supply of carbon dioxide a carbon yield of up to 96 % was achieved with the substrate sucrose.


  • Höfel T, Faust G, Reinecke L, Rudinger N, Weuster-Botz D (2012): Comparative reaction engineering studies for succinic acid production from sucrose by metabolically engineered Escherichia coli in fed-batch operated stirred tank bioreactors. Biotechnol J 7: 1277-1287.
  • Höfel T, Wittmann E, Reinecke L, Weuster-Botz D (2010): Reaction engineering studies for the production of 2-hydroxyisobutyric acid with recombinant Cupriavidus necator H16. Appl Microbiol Biotechnol 88: 477-484.