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

Heintz, Søren ; Börner, Tim LU ; Ringborg, Rolf H. ; Rehn, Gustav LU ; Grey, Carl LU orcid ; Nordblad, Mathias LU ; Krühne, Ulrich ; Gernaey, Krist V. LU ; Adlercreutz, Patrick LU orcid and Woodley, John M. (2017) In Biotechnology and Bioengineering 114(3). p.600-609
Abstract

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,... (More)

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.

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author
; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
amino transferase (ATAs), biocatalysis, chiral amines, in situ product removal (ISPR), process intensification, scale-down unit operations, substrate supply
in
Biotechnology and Bioengineering
volume
114
issue
3
pages
10 pages
publisher
John Wiley & Sons Inc.
external identifiers
  • scopus:84992451609
  • pmid:27668843
  • wos:000394606000012
ISSN
0006-3592
DOI
10.1002/bit.26191
language
English
LU publication?
yes
id
79a86f6f-a96b-4133-9ac2-f74ce364839d
date added to LUP
2017-02-03 08:46:27
date last changed
2025-01-07 05:52:05
@article{79a86f6f-a96b-4133-9ac2-f74ce364839d,
  abstract     = {{<p>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 g<sub>MPPA</sub> · L<sup>−1</sup>, a purity up to 70% g<sub>MPPA</sub> · g<sub>tot</sub>         <sup>−1</sup> and a recovery in the range of 80% mol · mol<sup>−1</sup> of MPPA in 20 h, with the possibility to increase the concentration, purity, and recovery further. Biotechnol. Bioeng. 2017;114: 600–609.</p>}},
  author       = {{Heintz, Søren and Börner, Tim and Ringborg, Rolf H. and Rehn, Gustav and Grey, Carl and Nordblad, Mathias and Krühne, Ulrich and Gernaey, Krist V. and Adlercreutz, Patrick and Woodley, John M.}},
  issn         = {{0006-3592}},
  keywords     = {{amino transferase (ATAs); biocatalysis; chiral amines; in situ product removal (ISPR); process intensification; scale-down unit operations; substrate supply}},
  language     = {{eng}},
  month        = {{03}},
  number       = {{3}},
  pages        = {{600--609}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{Biotechnology and Bioengineering}},
  title        = {{Development of in situ product removal strategies in biocatalysis applying scaled-down unit operations}},
  url          = {{http://dx.doi.org/10.1002/bit.26191}},
  doi          = {{10.1002/bit.26191}},
  volume       = {{114}},
  year         = {{2017}},
}