Unlocking the Potential of Trichoderma reesei as a Super‐Host for Heterologous Protein Production: Challenges, Advances, and Perspectives

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Auteurs principaux: Yu Li, Qinghao Wei, Mohd Sadeeq, Shibin Cui, Jia Zuo, Peng Xiong
Format: Artículo Open Access
Publié: Wiley 2025
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author Yu Li
Qinghao Wei
Mohd Sadeeq
Shibin Cui
Jia Zuo
Peng Xiong
author_facet Yu Li
Qinghao Wei
Mohd Sadeeq
Shibin Cui
Jia Zuo
Peng Xiong
Yu Li
Qinghao Wei
Mohd Sadeeq
Shibin Cui
Jia Zuo
Peng Xiong
collection Wiley Open Access
contents Unlocking the Potential of Trichoderma reesei as a Super‐Host for Heterologous Protein Production: Challenges, Advances, and Perspectives Yu Li Qinghao Wei Mohd Sadeeq Shibin Cui Jia Zuo Peng Xiong Biotechnology Journal ABSTRACTTrichoderma reesei, a filamentous fungus renowned for its exceptional secretion of cellulase. Its robust secretory capacity has sparked interest in its use as a host for producing heterologous proteins. However, yields of heterologous proteins remain critically low, presumably attributed to proteolytic degradation and the incompatibility of their robust transcription and secretory machinery, highly optimized for native cellulases with non‐native proteins.Strategies to enhance production are analyzed by reviewing nearly all the efforts, including promoter engineering to balance transcriptional strength with secretory capacity, signal peptide screening to modulate ER translocation efficiency, and fusing carrier proteins to bypass secretion bottlenecks. Proteolytic degradation as a major barrier has been mitigated through multi‐protease gene deletions, synergized with process optimization approaches like culture pH optimization and protease inhibitors. Additionally, the drawbacks of key strategies are critically analyzed, emphasizing the need for empirical validation of improvements and limitations for some strategies—or risk exclusion—before implementing specific approaches.Future research should focus on persistently developing genetically optimized strains with minimized protease activity, streamlined secretion pathways, and enhanced genetic manipulability. By systematically addressing these challenges, T. reesei could be engineered into a highly efficient host for the production of valuable proteins—from biofuels to therapeutics, advancing sustainable biomanufacturing. 10.1002/biot.70121 http://onlinelibrary.wiley.com/termsAndConditions#vor
doi_str_mv 10.1002/biot.70121
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spellingShingle Unlocking the Potential of Trichoderma reesei as a Super‐Host for Heterologous Protein Production: Challenges, Advances, and Perspectives
Yu Li
Qinghao Wei
Mohd Sadeeq
Shibin Cui
Jia Zuo
Peng Xiong
Biotechnology Journal
Unlocking the Potential of Trichoderma reesei as a Super‐Host for Heterologous Protein Production: Challenges, Advances, and Perspectives Yu Li Qinghao Wei Mohd Sadeeq Shibin Cui Jia Zuo Peng Xiong Biotechnology Journal ABSTRACTTrichoderma reesei, a filamentous fungus renowned for its exceptional secretion of cellulase. Its robust secretory capacity has sparked interest in its use as a host for producing heterologous proteins. However, yields of heterologous proteins remain critically low, presumably attributed to proteolytic degradation and the incompatibility of their robust transcription and secretory machinery, highly optimized for native cellulases with non‐native proteins.Strategies to enhance production are analyzed by reviewing nearly all the efforts, including promoter engineering to balance transcriptional strength with secretory capacity, signal peptide screening to modulate ER translocation efficiency, and fusing carrier proteins to bypass secretion bottlenecks. Proteolytic degradation as a major barrier has been mitigated through multi‐protease gene deletions, synergized with process optimization approaches like culture pH optimization and protease inhibitors. Additionally, the drawbacks of key strategies are critically analyzed, emphasizing the need for empirical validation of improvements and limitations for some strategies—or risk exclusion—before implementing specific approaches.Future research should focus on persistently developing genetically optimized strains with minimized protease activity, streamlined secretion pathways, and enhanced genetic manipulability. By systematically addressing these challenges, T. reesei could be engineered into a highly efficient host for the production of valuable proteins—from biofuels to therapeutics, advancing sustainable biomanufacturing. 10.1002/biot.70121 http://onlinelibrary.wiley.com/termsAndConditions#vor
title Unlocking the Potential of Trichoderma reesei as a Super‐Host for Heterologous Protein Production: Challenges, Advances, and Perspectives
topic Biotechnology Journal
url https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/10.1002/biot.70121