The Metabolic Building Blocks of a Minimal Cell

Defining the essential gene components for a system to be considered alive is a crucial step toward the synthesis of artificial life. Fifteen years ago, Gil and coworkers proposed the core of a putative minimal bacterial genome, which would provide the capability to achieve metabolic homeostasis, re...

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Main Authors: Mariana Reyes-Prieto, Rosario Gil, Mercè Llabrés, Pere Palmer-Rodríguez, Andrés Moya
Format: Article
Language:English
Published: MDPI AG 2020-12-01
Series:Biology
Subjects:
Online Access:https://www.mdpi.com/2079-7737/10/1/5
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author Mariana Reyes-Prieto
Rosario Gil
Mercè Llabrés
Pere Palmer-Rodríguez
Andrés Moya
author_facet Mariana Reyes-Prieto
Rosario Gil
Mercè Llabrés
Pere Palmer-Rodríguez
Andrés Moya
author_sort Mariana Reyes-Prieto
collection DOAJ
description Defining the essential gene components for a system to be considered alive is a crucial step toward the synthesis of artificial life. Fifteen years ago, Gil and coworkers proposed the core of a putative minimal bacterial genome, which would provide the capability to achieve metabolic homeostasis, reproduce, and evolve to a bacterium in an ideally controlled environment. They also proposed a simplified metabolic chart capable of providing energy and basic components for a minimal living cell. For this work, we have identified the components of the minimal metabolic network based on the aforementioned studies, associated them to the KEGG database and, by applying the MetaDAG methodology, determined its Metabolic Building Blocks (MBB) and reconstructed its metabolic Directed Acyclic Graph (m-DAG). The reaction graph of this metabolic network consists of 80 compounds and 98 reactions, while its m-DAG has 36 MBBs. Additionally, we identified 12 essential reactions in the m-DAG that are critical for maintaining the connectivity of this network. In a similar manner, we reconstructed the m-DAG of JCVI-syn3.0, which is an artificially designed and manufactured viable cell whose genome arose by minimizing the one from <i>Mycoplasma mycoides</i> JCVI-syn1.0, and of “<i>Candidatus</i> Nasuia deltocephalinicola”, the bacteria with the smallest natural genome known to date. The comparison of the m-DAGs derived from a theoretical, an artificial, and a natural genome denote slightly different lifestyles, with a consistent core metabolism. The MetaDAG methodology we employ uses homogeneous descriptors and identifiers from the KEGG database, so that comparisons between bacterial strains are not only easy but also suitable for many research fields. The modeling of m-DAGs based on minimal metabolisms can be the first step for the synthesis and manipulation of minimal cells.
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spelling doaj.art-fec668db519b45b7ad399963742a35f12023-11-21T02:20:37ZengMDPI AGBiology2079-77372020-12-01101510.3390/biology10010005The Metabolic Building Blocks of a Minimal CellMariana Reyes-Prieto0Rosario Gil1Mercè Llabrés2Pere Palmer-Rodríguez3Andrés Moya4Evolutionary Systems Biology of Symbionts, Institute for Integrative Systems Biology, University of Valencia and Spanish Research Council, Paterna, 46980 Valencia, SpainEvolutionary Systems Biology of Symbionts, Institute for Integrative Systems Biology, University of Valencia and Spanish Research Council, Paterna, 46980 Valencia, SpainDepartment of Mathematics and Computer Science, University of Balearic Islands, 07122 Palma de Mallorca, SpainDepartment of Mathematics and Computer Science, University of Balearic Islands, 07122 Palma de Mallorca, SpainEvolutionary Systems Biology of Symbionts, Institute for Integrative Systems Biology, University of Valencia and Spanish Research Council, Paterna, 46980 Valencia, SpainDefining the essential gene components for a system to be considered alive is a crucial step toward the synthesis of artificial life. Fifteen years ago, Gil and coworkers proposed the core of a putative minimal bacterial genome, which would provide the capability to achieve metabolic homeostasis, reproduce, and evolve to a bacterium in an ideally controlled environment. They also proposed a simplified metabolic chart capable of providing energy and basic components for a minimal living cell. For this work, we have identified the components of the minimal metabolic network based on the aforementioned studies, associated them to the KEGG database and, by applying the MetaDAG methodology, determined its Metabolic Building Blocks (MBB) and reconstructed its metabolic Directed Acyclic Graph (m-DAG). The reaction graph of this metabolic network consists of 80 compounds and 98 reactions, while its m-DAG has 36 MBBs. Additionally, we identified 12 essential reactions in the m-DAG that are critical for maintaining the connectivity of this network. In a similar manner, we reconstructed the m-DAG of JCVI-syn3.0, which is an artificially designed and manufactured viable cell whose genome arose by minimizing the one from <i>Mycoplasma mycoides</i> JCVI-syn1.0, and of “<i>Candidatus</i> Nasuia deltocephalinicola”, the bacteria with the smallest natural genome known to date. The comparison of the m-DAGs derived from a theoretical, an artificial, and a natural genome denote slightly different lifestyles, with a consistent core metabolism. The MetaDAG methodology we employ uses homogeneous descriptors and identifiers from the KEGG database, so that comparisons between bacterial strains are not only easy but also suitable for many research fields. The modeling of m-DAGs based on minimal metabolisms can be the first step for the synthesis and manipulation of minimal cells.https://www.mdpi.com/2079-7737/10/1/5metabolic networksminimal gene set machinerydirected acyclic graphsminimal cells
spellingShingle Mariana Reyes-Prieto
Rosario Gil
Mercè Llabrés
Pere Palmer-Rodríguez
Andrés Moya
The Metabolic Building Blocks of a Minimal Cell
Biology
metabolic networks
minimal gene set machinery
directed acyclic graphs
minimal cells
title The Metabolic Building Blocks of a Minimal Cell
title_full The Metabolic Building Blocks of a Minimal Cell
title_fullStr The Metabolic Building Blocks of a Minimal Cell
title_full_unstemmed The Metabolic Building Blocks of a Minimal Cell
title_short The Metabolic Building Blocks of a Minimal Cell
title_sort metabolic building blocks of a minimal cell
topic metabolic networks
minimal gene set machinery
directed acyclic graphs
minimal cells
url https://www.mdpi.com/2079-7737/10/1/5
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