Minimisation of metabolic networks defines a new functional class of genes

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Title: Minimisation of metabolic networks defines a new functional class of genes
Authors: Jansen, Giorgio, Qi, Tanda, Latora, Vito, Amoutzias, Grigoris D, Delneri, Daniela, Oliver, Stephen G, Nicosia, Giuseppe
Contributors: DSpace at Cambridge pro (8.1)
Source: Nat Commun
Nature Communications, Vol 15, Iss 1, Pp 1-11 (2024)
Jansen, G, Qi, T, Latora, V, Amoutzias, G D, Delneri, D & Nicosia, G 2024, 'Minimisation of metabolic networks defines a new functional class of genes', Nature Communications, vol. 15, no. 1, pp. 9076. https://doi.org/10.1038/s41467-024-52816-2
Publisher Information: Springer Science and Business Media LLC, 2024.
Publication Year: 2024
Subject Terms: Synthetic Biology/methods, Metabolic Networks and Pathways/genetics, Science, Computational Biology, Synthetic Biology, Computer Simulation, Saccharomyces cerevisiae, Computational Biology/methods, Article, Metabolic Networks and Pathways, Saccharomyces cerevisiae/genetics
Description: Construction of minimal metabolic networks (MMNs) contributes both to our understanding of the origins of metabolism and to the efficiency of biotechnological processes by preventing the diversion of flux away from product formation. We have designed MMNs using a novel in silico synthetic biology pipeline that removes genes encoding enzymes and transporters from genome-scale metabolic models. The resulting minimal gene-set still ensures both viability and high growth rates. The composition of these MMNs has defined a new functional class of genes termed Network Efficiency Determinants (NEDs). These genes, whilst not essential, are very rarely eliminated in constructing an MMN, suggesting that it is difficult for metabolism to be re-routed to obviate the need for such genes. Moreover, the removal of NED genes from an MMN significantly reduces its global efficiency. Bioinformatic analyses of the NED genes have revealed that not only do these genes have more genetic interactions than the bulk of metabolic genes but their protein products also show more protein-protein interactions. In yeast, NED genes are predominantly single-copy and are highly conserved across evolutionarily distant organisms. These features confirm the importance of the NED genes to the metabolic network, including why they are so rarely excluded during minimisation.
Document Type: Article
Other literature type
File Description: application/pdf; application/zip; text/xml; application/vnd.ms-excel
Language: English
ISSN: 2041-1723
DOI: 10.1038/s41467-024-52816-2
DOI: 10.17863/cam.112201
Access URL: https://pubmed.ncbi.nlm.nih.gov/39482321
https://doaj.org/article/8ab333ea3ee945a3b246aaf74a5e8aa1
https://hdl.handle.net/20.500.11769/652369
https://doi.org/10.1038/s41467-024-52816-2
https://www.nature.com/articles/s41467-024-52816-2
https://www.repository.cam.ac.uk/handle/1810/375664
https://doi.org/10.1038/s41467-024-52816-2
https://www.repository.cam.ac.uk/handle/1810/373980
https://doi.org/10.1038/s41467-024-52816-2
https://doi.org/10.17863/cam.112201
Rights: CC BY
Accession Number: edsair.doi.dedup.....61261ab0abeb8c822f8ce6275b781ae0
Database: OpenAIRE
Description
Abstract:Construction of minimal metabolic networks (MMNs) contributes both to our understanding of the origins of metabolism and to the efficiency of biotechnological processes by preventing the diversion of flux away from product formation. We have designed MMNs using a novel in silico synthetic biology pipeline that removes genes encoding enzymes and transporters from genome-scale metabolic models. The resulting minimal gene-set still ensures both viability and high growth rates. The composition of these MMNs has defined a new functional class of genes termed Network Efficiency Determinants (NEDs). These genes, whilst not essential, are very rarely eliminated in constructing an MMN, suggesting that it is difficult for metabolism to be re-routed to obviate the need for such genes. Moreover, the removal of NED genes from an MMN significantly reduces its global efficiency. Bioinformatic analyses of the NED genes have revealed that not only do these genes have more genetic interactions than the bulk of metabolic genes but their protein products also show more protein-protein interactions. In yeast, NED genes are predominantly single-copy and are highly conserved across evolutionarily distant organisms. These features confirm the importance of the NED genes to the metabolic network, including why they are so rarely excluded during minimisation.
ISSN:20411723
DOI:10.1038/s41467-024-52816-2