Development of in situ product removal strategies in biocatalysis applying scaled-down unit operations

Research output: Contribution to journalArticle


An experimental platform based on scaled-down unit operations combined in a plug-and-play manner enables easy and highly flexible testing of advanced biocatalytic process options such as in situ product removal (ISPR) process strategies. In such a platform, it is possible to compartmentalize different process steps while operating it as a combined system, giving the possibility to test and characterize the performance of novel process concepts and biocatalysts with minimal influence of inhibitory products. Here the capabilities of performing process development by applying scaled-down unit operations are highlighted through a case study investigating the asymmetric synthesis of 1-methyl-3-phenylpropylamine (MPPA) using ω-transaminase, an enzyme in the sub-family of amino transferases (ATAs). An on-line HPLC system was applied to avoid manual sample handling and to semi-automatically characterize ω-transaminases in a scaled-down packed-bed reactor (PBR) module, showing MPPA as a strong inhibitor. To overcome the inhibition, a two-step liquid–liquid extraction (LLE) ISPR concept was tested using scaled-down unit operations combined in a plug-and-play manner. Through the tested ISPR concept, it was possible to continuously feed the main substrate benzylacetone (BA) and extract the main product MPPA throughout the reaction, thereby overcoming the challenges of low substrate solubility and product inhibition. The tested ISPR concept achieved a product concentration of 26.5 gMPPA · L−1, a purity up to 70% gMPPA · gtot −1 and a recovery in the range of 80% mol · mol−1 of MPPA in 20 h, with the possibility to increase the concentration, purity, and recovery further. Biotechnol. Bioeng. 2017;114: 600–609.


  • Søren Heintz
  • Tim Börner
  • Rolf H. Ringborg
  • Gustav Rehn
  • Carl Grey
  • Mathias Nordblad
  • Ulrich Krühne
  • Krist V. Gernaey
  • Patrick Adlercreutz
  • John M. Woodley
External organisations
  • Technical University of Denmark
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Biocatalysis and Enzyme Technology


  • amino transferase (ATAs), biocatalysis, chiral amines, in situ product removal (ISPR), process intensification, scale-down unit operations, substrate supply
Original languageEnglish
Pages (from-to)600-609
Number of pages10
JournalBiotechnology and Bioengineering
Issue number3
Publication statusPublished - 2017 Mar 1
Publication categoryResearch