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


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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Fig. 1: Ultra-efficient closed-loop concept.
Fig. 2: Flow system assembly for the synthesis of primary alcohols.
Fig. 3: Synthesis of high-value alcohols from biogenic amines.
Fig. 4: Preparation of (S)-2-phenylpropanol from (R,S)-2-phenylpropylamine.
Fig. 5: Multienzymatic cascade synthesis of enantiopure (S)-1-phenylethanols.
Fig. 6: Ultra-efficient multienzyme conversion of amines into alcohols.


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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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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.

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Correspondence to Francesca Paradisi.

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Supplementary Information

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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Contente, M.L., Paradisi, F. Self-sustaining closed-loop multienzyme-mediated conversion of amines into alcohols in continuous reactions. Nat Catal 1, 452–459 (2018).

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