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Self-sustaining closed-loop multienzyme-mediated conversion of amines into alcohols in continuous reactions

Nature Catalysisvolume 1pages452459 (2018) | Download Citation


The synthesis of alcohols from amine starting materials is an excellent yet challenging strategy for the preparation of pharmaceuticals and polymers. Here we developed a versatile, self-sustaining closed-loop multienzymatic platform for the biocatalytic synthesis of a large range of non-commercially available products in a continuous flow with excellent yields (80 to >99%), reaction times and optical purity of secondary alcohols (>99 enantiomeric excess). This process was also extended to the conversion of biogenic amines into high-value alcohols, such as the powerful antioxidant hydroxytyrosol, and the synthesis of enantiopure 2-arylpropanols via the dynamic kinetic resolution of commercially affordable racemic amines. The system exploits the in situ immobilization of transaminases and redox enzymes which were combined to cater for a fully automated, ultra-efficient synthetic platform with cofactor recycling, in-line recovery of benign by-products and recirculation of the aqueous media that contains the recycled cofactors in catalytic amounts, which increases the efficiency of the system by over 20-fold.

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This work was supported by the Biotechnology and Biological Sciences Research Council [grant no. BB/P002536/1]; and the authors thank Resindion S.R.L. for donating the Sepabeads EC-EP/S.

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  1. School of Chemistry, University of Nottingham, Nottingham, United Kingdom

    • Martina L. Contente
    •  & Francesca Paradisi


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M.L.C. performed the experimental work and analysed the results. M.L.C. and F.P. conceived and designed the experiments. M.L.C. and F.P. co-wrote the manuscript.

Competing interests

The authors declare no competing interests.

Corresponding author

Correspondence to Francesca Paradisi.

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    Supplementary Methods, Supplementary Tables 1–4, Supplementary Equations 1 and 2, Supplementary Figures 1–3, Supplementary Note 1, Supplementary References, NMR Spectra

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