Synergies in Green Bioprocessing: A Comprehensive Review of Heterologous Protein Expression and the Transformative Potential of Natural Deep Eutectic Solvents

[Data Availability Statement] No new data were created or analyzed in this study.

Detalles Bibliográficos
Autores: Martínez-Olivares, José Agustín, Coca Ruiz, Víctor
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/404699
Acceso en línea:http://hdl.handle.net/10261/404699
Access Level:acceso abierto
Palabra clave:Heterologous expression
Recombinant protein
Natural deep eutectic solvents (NADESs)
Green solvents
Inclusion bodies
Protein refolding
Aqueous two-phase system (ATPS)
Biocatalysis
Escherichia coli
Pichia pastoris
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spelling Synergies in Green Bioprocessing: A Comprehensive Review of Heterologous Protein Expression and the Transformative Potential of Natural Deep Eutectic SolventsMartínez-Olivares, José AgustínCoca Ruiz, VíctorHeterologous expressionRecombinant proteinNatural deep eutectic solvents (NADESs)Green solventsInclusion bodiesProtein refoldingAqueous two-phase system (ATPS)BiocatalysisEscherichia coliPichia pastoris[Data Availability Statement] No new data were created or analyzed in this study.Heterologous protein expression underpins the production of therapeutics, industrial enzymes, and diagnostic reagents, yet persistent challenges remain in enhancing yields, achieving correct folding, and reducing the costs and environmental burdens of downstream processing. Natural Deep Eutectic Solvents (NADESs)—a class of biocompatible, sustainable, and highly tunable solvents—have recently emerged as promising tools to overcome these limitations. This review systematically examines the intersection of recombinant protein production and NADES technology, assessing their applications across the full workflow, from host strain expression to purification and final formulation. Literature analysis highlights the potential of NADESs as media additives that mitigate cellular stress and improve soluble protein yields, as gentle solubilizing and refolding agents for inclusion bodies, as phase-forming components in aqueous two-phase systems for green purification, and as stabilizing excipients for long-term storage. Key constituents such as betaine, proline, urea, and arginine are identified as functional agents whose eutectic mixtures often deliver synergistic benefits that differ mechanistically from the action of the individual components. The integration of NADESs into recombinant protein production offers a path toward more sustainable and economically viable biomanufacturing. Critical gaps remain, including in vivo validation and techno-economic assessment. Future opportunities include high-throughput NADES screening and computational design of application-specific solvents.This research received no external funding.Peer reviewedMultidisciplinary Digital Publishing InstituteMartínez-Olivares, José Agustín [0009-0001-0517-9439]Coca Ruiz, Víctor [0000-0001-9576-1205]Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2025202520252025info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_dcae04bcPublisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/404699reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttps://doi.org/10.3390/applmicrobiol5040113Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/4046992026-05-22T06:33:51Z
dc.title.none.fl_str_mv Synergies in Green Bioprocessing: A Comprehensive Review of Heterologous Protein Expression and the Transformative Potential of Natural Deep Eutectic Solvents
title Synergies in Green Bioprocessing: A Comprehensive Review of Heterologous Protein Expression and the Transformative Potential of Natural Deep Eutectic Solvents
spellingShingle Synergies in Green Bioprocessing: A Comprehensive Review of Heterologous Protein Expression and the Transformative Potential of Natural Deep Eutectic Solvents
Martínez-Olivares, José Agustín
Heterologous expression
Recombinant protein
Natural deep eutectic solvents (NADESs)
Green solvents
Inclusion bodies
Protein refolding
Aqueous two-phase system (ATPS)
Biocatalysis
Escherichia coli
Pichia pastoris
title_short Synergies in Green Bioprocessing: A Comprehensive Review of Heterologous Protein Expression and the Transformative Potential of Natural Deep Eutectic Solvents
title_full Synergies in Green Bioprocessing: A Comprehensive Review of Heterologous Protein Expression and the Transformative Potential of Natural Deep Eutectic Solvents
title_fullStr Synergies in Green Bioprocessing: A Comprehensive Review of Heterologous Protein Expression and the Transformative Potential of Natural Deep Eutectic Solvents
title_full_unstemmed Synergies in Green Bioprocessing: A Comprehensive Review of Heterologous Protein Expression and the Transformative Potential of Natural Deep Eutectic Solvents
title_sort Synergies in Green Bioprocessing: A Comprehensive Review of Heterologous Protein Expression and the Transformative Potential of Natural Deep Eutectic Solvents
dc.creator.none.fl_str_mv Martínez-Olivares, José Agustín
Coca Ruiz, Víctor
author Martínez-Olivares, José Agustín
author_facet Martínez-Olivares, José Agustín
Coca Ruiz, Víctor
author_role author
author2 Coca Ruiz, Víctor
author2_role author
dc.contributor.none.fl_str_mv Martínez-Olivares, José Agustín [0009-0001-0517-9439]
Coca Ruiz, Víctor [0000-0001-9576-1205]
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Heterologous expression
Recombinant protein
Natural deep eutectic solvents (NADESs)
Green solvents
Inclusion bodies
Protein refolding
Aqueous two-phase system (ATPS)
Biocatalysis
Escherichia coli
Pichia pastoris
topic Heterologous expression
Recombinant protein
Natural deep eutectic solvents (NADESs)
Green solvents
Inclusion bodies
Protein refolding
Aqueous two-phase system (ATPS)
Biocatalysis
Escherichia coli
Pichia pastoris
description [Data Availability Statement] No new data were created or analyzed in this study.
publishDate 2025
dc.date.none.fl_str_mv 2025
2025
2025
2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_dcae04bc
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/404699
url http://hdl.handle.net/10261/404699
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv https://doi.org/10.3390/applmicrobiol5040113
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812455

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