Cargando…
The Metabolic Building Blocks of a Minimal Cell
SIMPLE SUMMARY: Manufacturing artificial living cells would open endless research possibilities in basic and applied sciences. With this motivation, many research groups are developing methodologies to construct a stable minimal cell that is capable of achieving metabolic homeostasis, reproducing, a...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7824019/ https://www.ncbi.nlm.nih.gov/pubmed/33374107 http://dx.doi.org/10.3390/biology10010005 |
_version_ | 1783639975219167232 |
---|---|
author | Reyes-Prieto, Mariana Gil, Rosario Llabrés, Mercè Palmer-Rodríguez, Pere Moya, Andrés |
author_facet | Reyes-Prieto, Mariana Gil, Rosario Llabrés, Mercè Palmer-Rodríguez, Pere Moya, Andrés |
author_sort | Reyes-Prieto, Mariana |
collection | PubMed |
description | SIMPLE SUMMARY: Manufacturing artificial living cells would open endless research possibilities in basic and applied sciences. With this motivation, many research groups are developing methodologies to construct a stable minimal cell that is capable of achieving metabolic homeostasis, reproducing, and evolving in a controlled environment. Using as a template the gene set for a minimal cell proposed previously by Gil and coworkers, we have put together a network depicting its inferred minimal metabolism needed for life. This network has been further compressed as a metabolic Directed Acyclic Graph (m-DAG) in order to better visualize its topology and to find its essential reactions (i.e., critical reactions to maintain the network’s connectivity). We have also compared this minimal m-DAG to those of the smallest natural genome known until now and a synthetic minimal cell created in the laboratory. The modeling of m-DAGs based on minimal metabolisms can be a first approach for the synthesis and manipulation of minimal cells. ABSTRACT: 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 Mycoplasma mycoides JCVI-syn1.0, and of “Candidatus 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. |
format | Online Article Text |
id | pubmed-7824019 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-78240192021-01-24 The Metabolic Building Blocks of a Minimal Cell Reyes-Prieto, Mariana Gil, Rosario Llabrés, Mercè Palmer-Rodríguez, Pere Moya, Andrés Biology (Basel) Article SIMPLE SUMMARY: Manufacturing artificial living cells would open endless research possibilities in basic and applied sciences. With this motivation, many research groups are developing methodologies to construct a stable minimal cell that is capable of achieving metabolic homeostasis, reproducing, and evolving in a controlled environment. Using as a template the gene set for a minimal cell proposed previously by Gil and coworkers, we have put together a network depicting its inferred minimal metabolism needed for life. This network has been further compressed as a metabolic Directed Acyclic Graph (m-DAG) in order to better visualize its topology and to find its essential reactions (i.e., critical reactions to maintain the network’s connectivity). We have also compared this minimal m-DAG to those of the smallest natural genome known until now and a synthetic minimal cell created in the laboratory. The modeling of m-DAGs based on minimal metabolisms can be a first approach for the synthesis and manipulation of minimal cells. ABSTRACT: 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 Mycoplasma mycoides JCVI-syn1.0, and of “Candidatus 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. MDPI 2020-12-24 /pmc/articles/PMC7824019/ /pubmed/33374107 http://dx.doi.org/10.3390/biology10010005 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Reyes-Prieto, Mariana Gil, Rosario Llabrés, Mercè Palmer-Rodríguez, Pere Moya, Andrés The Metabolic Building Blocks of a Minimal Cell |
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 | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7824019/ https://www.ncbi.nlm.nih.gov/pubmed/33374107 http://dx.doi.org/10.3390/biology10010005 |
work_keys_str_mv | AT reyesprietomariana themetabolicbuildingblocksofaminimalcell AT gilrosario themetabolicbuildingblocksofaminimalcell AT llabresmerce themetabolicbuildingblocksofaminimalcell AT palmerrodriguezpere themetabolicbuildingblocksofaminimalcell AT moyaandres themetabolicbuildingblocksofaminimalcell AT reyesprietomariana metabolicbuildingblocksofaminimalcell AT gilrosario metabolicbuildingblocksofaminimalcell AT llabresmerce metabolicbuildingblocksofaminimalcell AT palmerrodriguezpere metabolicbuildingblocksofaminimalcell AT moyaandres metabolicbuildingblocksofaminimalcell |