Issue 7, 2023

Continuous flow-mode synthesis of (chiral) amines with transaminase: a strategic biocatalytic approach to essential building blocks

Abstract

Chiral amines are essential building blocks to manufacture a plethora of valuable compounds, including active pharmaceutical ingredients (API). It is estimated that about half of the current API contain chiral amines in their structure. However, the current production of chiral amines often involves multi-step synthesis requiring expensive homogeneous catalysts and high energy consumption for subsequent purification. Biocatalytic routes have gained considerable attention in the last decades, as effective and potentially more sustainable alternatives. Indeed, amine transaminases (ATAs) can catalyse transamination reactions and produce chiral amines with excellent enantioselectivity and in mild conditions. Industrial applications of biocatalytic transamination, however, remain scarce as the enzymes often operate in restricted operational conditions and display limited stability. Batch reactors utilizing the free enzyme in solution also face issues regarding catalyst separation, recovery, and reuse. Moreover, the synthesis of most compounds of interest is thermodynamically unfavoured. Taking a side step, catalysis scientists design heterogenized biocatalysts that are more versatile, more stable, and amenable to continuous flow processes. A number of improvement strategies have been deployed: modifications of the transaminase itself (via genetic engineering), optimization of immobilization strategies, design of structured supports, development of integrated equilibrium shifting strategies, concatenation with purification, etc. Here, we summarize and exemplify these advances leading to more efficient biocatalytic systems based on transaminases operating in continuous flow mode.

Graphical abstract: Continuous flow-mode synthesis of (chiral) amines with transaminase: a strategic biocatalytic approach to essential building blocks

Article information

Article type
Review Article
Submitted
06 abr. 2023
Accepted
19 may. 2023
First published
22 may. 2023

React. Chem. Eng., 2023,8, 1505-1544

Continuous flow-mode synthesis of (chiral) amines with transaminase: a strategic biocatalytic approach to essential building blocks

H. Meersseman Arango, L. van den Biggelaar, P. Soumillion, P. Luis, T. Leyssens, F. Paradisi and D. P. Debecker, React. Chem. Eng., 2023, 8, 1505 DOI: 10.1039/D3RE00210A

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements