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http://hdl.handle.net/10261/330763
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dc.contributor.author | Wirth, Nicolas T. | es_ES |
dc.contributor.author | Gurdo, Nicolás | es_ES |
dc.contributor.author | Krink, Nicolas | es_ES |
dc.contributor.author | Vidal‐Verdú, Ángela | es_ES |
dc.contributor.author | Donati, Stefano | es_ES |
dc.contributor.author | Férnandez-Cabezón, Lorena | es_ES |
dc.contributor.author | Wulff, Tune | es_ES |
dc.contributor.author | Nikel, Pablo I. | es_ES |
dc.date.accessioned | 2023-07-10T09:57:01Z | - |
dc.date.available | 2023-07-10T09:57:01Z | - |
dc.date.issued | 2022 | - |
dc.identifier.citation | Metabolic Engineering 74: 83-97 (2022) | es_ES |
dc.identifier.issn | 1096-7184 | - |
dc.identifier.uri | http://hdl.handle.net/10261/330763 | - |
dc.description.abstract | Acetyl-coenzyme A (AcCoA) is a metabolic hub in virtually all living cells, serving as both a key precursor of essential biomass components and a metabolic sink for catabolic pathways for a large variety of substrates. Owing to this dual role, tight growth-production coupling schemes can be implemented around the AcCoA node. Building on this concept, a synthetic C2 auxotrophy was implemented in the platform bacterium Pseudomonas putida through an in silico-informed engineering approach. A growth-coupling strategy, driven by AcCoA demand, allowed for direct selection of an alternative sugar assimilation route—the phosphoketolase (PKT) shunt from bifidobacteria. Adaptive laboratory evolution forced the synthetic P. putida auxotroph to rewire its metabolic network to restore C2 prototrophy via the PKT shunt. Large-scale structural chromosome rearrangements were identified as possible mechanisms for adjusting the network-wide proteome profile, resulting in improved PKT-dependent growth phenotypes. 13C-based metabolic flux analysis revealed an even split between the native Entner-Doudoroff pathway and the synthetic PKT bypass for glucose processing, leading to enhanced carbon conservation. These results demonstrate that the P. putida metabolism can be radically rewired to incorporate a synthetic C2 metabolism, creating novel network connectivities and highlighting the importance of unconventional engineering strategies to support efficient microbial production. | es_ES |
dc.description.sponsorship | L.F.C. was supported by the European Union's Horizon 2020 Research and Innovation Programme under the Marie Skłodowska-Curie grant agreement No. 839839 (DONNA). The financial support from The Novo Nordisk Foundation through grants NNF20CC0035580, LiFe (NNF18OC0034818) and TARGET (NNF21OC0067996), the Danish Council for Independent Research (SWEET, DFF-Research Project 8021-00039B), and the European Union's Horizon 2020 Research and Innovation Programme under grant agreement No. 814418 (SinFonia) to P.I.N. is likewise gratefully acknowledged. | es_ES |
dc.format | application/pdf | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Elsevier | es_ES |
dc.relation | info:eu-repo/grantAgreement/EC/H2020/814418 | es_ES |
dc.relation | info:eu-repo/grantAgreement/EC/H2020/839839 | es_ES |
dc.relation.isversionof | Publisher's version | es_ES |
dc.rights | openAccess | es_ES |
dc.subject | Metabolic engineering | es_ES |
dc.subject | Pseudomonas putida | es_ES |
dc.subject | Synthetic biology | es_ES |
dc.subject | Synthetic metabolism | es_ES |
dc.subject | Synthetic auxotrophy | es_ES |
dc.subject | Phosphoketolase | es_ES |
dc.title | A synthetic C2 auxotroph of Pseudomonas putida for evolutionary engineering of alternative sugar catabolic routes | es_ES |
dc.type | artículo | es_ES |
dc.identifier.doi | 10.1016/j.ymben.2022.09.004 | - |
dc.description.peerreviewed | Peer reviewed | es_ES |
dc.relation.publisherversion | https://doi.org/10.1016/j.ymben.2022.09.004 | es_ES |
dc.rights.license | http://creativecommons.org/licenses/by/4.0/ | es_ES |
dc.contributor.funder | European Commission | es_ES |
dc.contributor.funder | Novo Nordisk Foundation | es_ES |
dc.contributor.funder | Danish Council for Independent Research | es_ES |
dc.relation.csic | Sí | es_ES |
oprm.item.hasRevision | no ko 0 false | * |
dc.identifier.funder | http://dx.doi.org/10.13039/501100000780 | es_ES |
dc.identifier.pmid | 36155822 | - |
dc.type.coar | http://purl.org/coar/resource_type/c_6501 | es_ES |
item.openairetype | artículo | - |
item.languageiso639-1 | en | - |
item.fulltext | With Fulltext | - |
item.grantfulltext | open | - |
item.cerifentitytype | Publications | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
Aparece en las colecciones: | (I2SysBio) Artículos |
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catabolicroutes.pdf | 6,13 MB | Adobe PDF | Visualizar/Abrir |
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