A refined picture of the native Amine Dehydrogenase family revealed by extensive biodiversity screening

Gideon James Grogan; Eddy Elisee; Laurine  Ducrot; Raphael Meheust; Karine Bastard; Aurelie Fossey-Jouenne; Eric Pelletier; Jean-Louis Petit; Mark Stam; Veronique de Berardinis; Anne Zaparucha; David Vallenet; Carine Vergne-Vaxelaire

doi:10.1038/s41467-024-49009-2

A refined picture of the native Amine Dehydrogenase family revealed by extensive biodiversity screening

Gideon James Grogan, Eddy Elisee, Laurine Ducrot, Raphael Meheust, Karine Bastard, Aurelie Fossey-Jouenne, Eric Pelletier, Jean-Louis Petit, Mark Stam, Veronique de Berardinis, Anne Zaparucha, David Vallenet, Carine Vergne-Vaxelaire

Chemistry

Research output: Contribution to journal › Article › peer-review

Abstract

Native amine dehydrogenases offer sustainable access to chiral amines, so the search for scaffolds capable of converting more diverse carbonyl compounds is required to reach the full potential of this alternative to conventional synthetic reductive aminations. Here we report a multidisciplinary strategy combining bioinformatics, chemoinformatics and biocatalysis to extensively screen billions of sequences in silico and to efficiently find native amine dehydrogenases features using computational approaches. In this way, we achieve a comprehensive overview of the initial native amine dehydrogenase family, extending it from 2,011 to 17,959 sequences, and identify native amine dehydrogenases with non-reported substrate spectra, including hindered carbonyls and ethyl ketones, and accepting methylamine and cyclopropylamine as amine donor. We also present preliminary model-based structural information to inform the design of potential (R)-selective amine dehydrogenases, as native amine dehydrogenases are mostly (S)-selective. This integrated strategy paves the way for expanding the resource of other enzyme families and in highlighting enzymes with original features.
INTRODUCTION

Original language	English
Article number	4933
Number of pages	15
Journal	Nature Communications
Volume	15
DOIs	https://doi.org/10.1038/s41467-024-49009-2
Publication status	Published - 10 Jun 2024

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A refined picture of the native Amine Dehydrogenase family revealed by extensive biodiversity screening
© The Author(s) 2024
Final published version, 2.55 MBLicence: CC BY

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Grogan, G. J., Elisee, E., Ducrot, L., Meheust, R., Bastard, K., Fossey-Jouenne, A., Pelletier, E., Petit, J.-L., Stam, M., de Berardinis, V., Zaparucha, A., Vallenet, D., & Vergne-Vaxelaire, C. (2024). A refined picture of the native Amine Dehydrogenase family revealed by extensive biodiversity screening. Nature Communications, 15, Article 4933. https://doi.org/10.1038/s41467-024-49009-2

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abstract = "Native amine dehydrogenases offer sustainable access to chiral amines, so the search for scaffolds capable of converting more diverse carbonyl compounds is required to reach the full potential of this alternative to conventional synthetic reductive aminations. Here we report a multidisciplinary strategy combining bioinformatics, chemoinformatics and biocatalysis to extensively screen billions of sequences in silico and to efficiently find native amine dehydrogenases features using computational approaches. In this way, we achieve a comprehensive overview of the initial native amine dehydrogenase family, extending it from 2,011 to 17,959 sequences, and identify native amine dehydrogenases with non-reported substrate spectra, including hindered carbonyls and ethyl ketones, and accepting methylamine and cyclopropylamine as amine donor. We also present preliminary model-based structural information to inform the design of potential (R)-selective amine dehydrogenases, as native amine dehydrogenases are mostly (S)-selective. This integrated strategy paves the way for expanding the resource of other enzyme families and in highlighting enzymes with original features.INTRODUCTION",

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Grogan, GJ, Elisee, E, Ducrot, L, Meheust, R, Bastard, K, Fossey-Jouenne, A, Pelletier, E, Petit, J-L, Stam, M, de Berardinis, V, Zaparucha, A, Vallenet, D & Vergne-Vaxelaire, C 2024, 'A refined picture of the native Amine Dehydrogenase family revealed by extensive biodiversity screening', Nature Communications, vol. 15, 4933. https://doi.org/10.1038/s41467-024-49009-2

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T1 - A refined picture of the native Amine Dehydrogenase family revealed by extensive biodiversity screening

AU - Grogan, Gideon James

AU - Elisee, Eddy

AU - Ducrot, Laurine

AU - Meheust, Raphael

AU - Bastard, Karine

AU - Fossey-Jouenne, Aurelie

AU - Pelletier, Eric

AU - Petit, Jean-Louis

AU - Stam, Mark

AU - de Berardinis, Veronique

AU - Zaparucha, Anne

AU - Vallenet, David

AU - Vergne-Vaxelaire, Carine

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AB - Native amine dehydrogenases offer sustainable access to chiral amines, so the search for scaffolds capable of converting more diverse carbonyl compounds is required to reach the full potential of this alternative to conventional synthetic reductive aminations. Here we report a multidisciplinary strategy combining bioinformatics, chemoinformatics and biocatalysis to extensively screen billions of sequences in silico and to efficiently find native amine dehydrogenases features using computational approaches. In this way, we achieve a comprehensive overview of the initial native amine dehydrogenase family, extending it from 2,011 to 17,959 sequences, and identify native amine dehydrogenases with non-reported substrate spectra, including hindered carbonyls and ethyl ketones, and accepting methylamine and cyclopropylamine as amine donor. We also present preliminary model-based structural information to inform the design of potential (R)-selective amine dehydrogenases, as native amine dehydrogenases are mostly (S)-selective. This integrated strategy paves the way for expanding the resource of other enzyme families and in highlighting enzymes with original features.INTRODUCTION

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