Current state of molecular and metabolic strategies for the improvement of L-asparaginase expression in heterologous systems
Heterologous expression of L-asparaginase (L-ASNase) has become an important area of research due to its clinical and food industry applications. This review provides a comprehensive overview of the molecular and metabolic strategies that can be used to optimize the expression of L-ASNase in heterol...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-06-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2023.1208277/full |
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| author | Nicolás Lefin Javiera Miranda Jorge F. Beltrán Lisandra Herrera Belén Brian Effer Adalberto Pessoa Jorge G. Farias Mauricio Zamorano |
| author_facet | Nicolás Lefin Javiera Miranda Jorge F. Beltrán Lisandra Herrera Belén Brian Effer Adalberto Pessoa Jorge G. Farias Mauricio Zamorano |
| author_sort | Nicolás Lefin |
| collection | DOAJ |
| description | Heterologous expression of L-asparaginase (L-ASNase) has become an important area of research due to its clinical and food industry applications. This review provides a comprehensive overview of the molecular and metabolic strategies that can be used to optimize the expression of L-ASNase in heterologous systems. This article describes various approaches that have been employed to increase enzyme production, including the use of molecular tools, strain engineering, and in silico optimization. The review article highlights the critical role that rational design plays in achieving successful heterologous expression and underscores the challenges of large-scale production of L-ASNase, such as inadequate protein folding and the metabolic burden on host cells. Improved gene expression is shown to be achievable through the optimization of codon usage, synthetic promoters, transcription and translation regulation, and host strain improvement, among others. Additionally, this review provides a deep understanding of the enzymatic properties of L-ASNase and how this knowledge has been employed to enhance its properties and production. Finally, future trends in L-ASNase production, including the integration of CRISPR and machine learning tools are discussed. This work serves as a valuable resource for researchers looking to design effective heterologous expression systems for L-ASNase production as well as for enzymes production in general. |
| first_indexed | 2024-03-13T03:55:12Z |
| format | Article |
| id | doaj.art-bbc9b3a9fbac46e0ba0fc5b208e388f2 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-03-13T03:55:12Z |
| publishDate | 2023-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-bbc9b3a9fbac46e0ba0fc5b208e388f22023-06-22T05:59:14ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122023-06-011410.3389/fphar.2023.12082771208277Current state of molecular and metabolic strategies for the improvement of L-asparaginase expression in heterologous systemsNicolás Lefin0Javiera Miranda1Jorge F. Beltrán2Lisandra Herrera Belén3Brian Effer4Adalberto Pessoa5Jorge G. Farias6Mauricio Zamorano7Department of Chemical Engineering, Science and Engineering Faculty, Universidad de La Frontera, Temuco, ChileDepartment of Chemical Engineering, Science and Engineering Faculty, Universidad de La Frontera, Temuco, ChileDepartment of Chemical Engineering, Science and Engineering Faculty, Universidad de La Frontera, Temuco, ChileDepartamento de Ciencias Básicas, Facultad de Ciencias, Universidad Santo Tomas, Santiago, ChileCenter of Excellence in Translational Medicine and Scientific and Technological Bioresource Nucleus, Universidad de La Frontera, Temuco, ChileDepartment of Biochemical and Pharmaceutical Technology, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, BrazilDepartment of Chemical Engineering, Science and Engineering Faculty, Universidad de La Frontera, Temuco, ChileDepartment of Chemical Engineering, Science and Engineering Faculty, Universidad de La Frontera, Temuco, ChileHeterologous expression of L-asparaginase (L-ASNase) has become an important area of research due to its clinical and food industry applications. This review provides a comprehensive overview of the molecular and metabolic strategies that can be used to optimize the expression of L-ASNase in heterologous systems. This article describes various approaches that have been employed to increase enzyme production, including the use of molecular tools, strain engineering, and in silico optimization. The review article highlights the critical role that rational design plays in achieving successful heterologous expression and underscores the challenges of large-scale production of L-ASNase, such as inadequate protein folding and the metabolic burden on host cells. Improved gene expression is shown to be achievable through the optimization of codon usage, synthetic promoters, transcription and translation regulation, and host strain improvement, among others. Additionally, this review provides a deep understanding of the enzymatic properties of L-ASNase and how this knowledge has been employed to enhance its properties and production. Finally, future trends in L-ASNase production, including the integration of CRISPR and machine learning tools are discussed. This work serves as a valuable resource for researchers looking to design effective heterologous expression systems for L-ASNase production as well as for enzymes production in general.https://www.frontiersin.org/articles/10.3389/fphar.2023.1208277/fullL-asparaginasemolecular strategiesrational designheterologous expression systemindustrial bioprocessing |
| spellingShingle | Nicolás Lefin Javiera Miranda Jorge F. Beltrán Lisandra Herrera Belén Brian Effer Adalberto Pessoa Jorge G. Farias Mauricio Zamorano Current state of molecular and metabolic strategies for the improvement of L-asparaginase expression in heterologous systems Frontiers in Pharmacology L-asparaginase molecular strategies rational design heterologous expression system industrial bioprocessing |
| title | Current state of molecular and metabolic strategies for the improvement of L-asparaginase expression in heterologous systems |
| title_full | Current state of molecular and metabolic strategies for the improvement of L-asparaginase expression in heterologous systems |
| title_fullStr | Current state of molecular and metabolic strategies for the improvement of L-asparaginase expression in heterologous systems |
| title_full_unstemmed | Current state of molecular and metabolic strategies for the improvement of L-asparaginase expression in heterologous systems |
| title_short | Current state of molecular and metabolic strategies for the improvement of L-asparaginase expression in heterologous systems |
| title_sort | current state of molecular and metabolic strategies for the improvement of l asparaginase expression in heterologous systems |
| topic | L-asparaginase molecular strategies rational design heterologous expression system industrial bioprocessing |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2023.1208277/full |
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