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Poster De Conférence Année : 2022

An integrative bioinformatics approach to explore the biodiversity of enzyme families

Résumé

Introduction Metagenomics data represent a largely untapped and continuously growing pool of new sequences coming from various worldwide biotopes (soil, human gut, oceans…). This biodiversity, up to several billions of sequences, may be exploited to answer multiple scientific challenges. For instance, biocatalysis (i.e. catalysis with enzymes) needs new relevant biocatalysts with various activities to take up the energy transition challenge and replace some polluting synthesis steps. Hence, bioinformatics approaches to efficiently identify the targeted enzymatic activity from large metagenomic resources are needed. Through the MODAMDH project (ANR JCJC), we focused on one of the key biocatalysts named amine dehydrogenases (AmDHs) which enable the access to amines that are important entities in the chemical industry [1-2]. To do so, we applied a sequence- and structure-based bioinformatics approach to widen the landscape of protein sequences catalyzing reductive amination by searching for remote homologs and active site analogs. In the context of the ALADIN project (ESR / EquipEx+), we want to generalize this approach and develop workflows that could be applied to any enzyme family. Methods Publicly available and in-house metagenomics databases (>2.5 billion protein sequences) were screened using HMMER software and the SUPERFAMILY database. Structural modeling and active site classification were performed by the ASMC software [3]. Remote homologs were recovered by HMM-HMM comparisons with HHblits software. Active site analogs were searched by screening catalophores (i.e. minimal active site topologies) using the YASARA software. Phylogeny of protein families was done with IQ-TREE program. Results The AmDH family was first enriched with new metagenomic sequences before being classified into subfamilies using an active site classification and a phylogeny. Besides, we generated a pool of NAD(P)-binding protein sequences from which we found, using HMM-HMM comparisons, new AmDH distant homologs. In contrast, no active site analog has yet been found for the AmDH family. Through the ALADIN project, we will extend this strategy to other enzymatic activities by designing generic workflows and applying them first to explore the diversity of the aforementioned NAD(P)-binding protein families. Acknowledgements This study was supported by the contracts from the MODAMDH (ANR-19-CE07-0007, ANR JCJC) and ALADIN (IA-21-ESRE-0021, ESR / EquipEx+) projects.
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hal-04360074 , version 1 (21-12-2023)

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  • HAL Id : hal-04360074 , version 1

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Elisée Eddy, Mark Stam, Raphaël Méheust, Carine Vergne-Vaxelaire, David Vallenet. An integrative bioinformatics approach to explore the biodiversity of enzyme families. Journées Ouvertes en Biologie, Informatique et Mathématiques (JOBIM) 2022, Jul 2022, Rennes, France. ⟨hal-04360074⟩
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