ArticlePloS one2015
Enabling Low Cost Biopharmaceuticals: A Systematic Approach to Delete Proteases from a Well-Known Protein Production Host Trichoderma reesei.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 72 citations in OpenAlex.
- Design and Heterologous Production of Bagworm Silk-Inspired Proteins inComputational and structural biotechnology journal · 2026Article
- The landscape of antibody production systems: recombinant expression for research, diagnostics and therapy.Frontiers in bioengineering and biotechnology · 2026Review
- Improving recombinant protein secretion inMetabolic engineering communications · 2025Article
- Improving therapeutic protein secretion in the probiotic yeast Saccharomyces boulardii using a multifactorial engineering approach.Microbial cell factories · 2023Article
- Inducer-free recombinant protein production in Trichoderma reesei: secretory production of endogenous enzymes and heterologous nanobodies using glucose as the sole carbon source.Microbial cell factories · 2023Article
- Functional characterization of a highly specific L-arabinose transporter from Trichoderma reesei.Microbial cell factories · 2021Article
- Understanding the Role ofJournal of fungi (Basel, Switzerland) · 2021Article
- Harnessing microbial wealth for lignocellulose biomass valorization through secretomics: a review.Biotechnology for biofuels · 2021Review
- Characterization of the effects of terminators and introns on recombinant gene expression in the basidiomycete Ceriporiopsis subvermispora.Journal of microbiology (Seoul, Korea) · 2020Article
- Involvement of Xyr1 and Are1 for Trichodermapepsin Gene Expression in Response to Cellulose and Galactose in Trichoderma reesei.Current microbiology · 2020Article
- Studies on sugar transporter CRT1 reveal new characteristics that are critical for cellulase induction inBiotechnology for biofuels · 2020Article
- Rational engineering of theBiotechnology for biofuels · 2020Article
- WY195, a New Inducible Promoter From the Rubber Powdery Mildew Pathogen, Can Be Used as an Excellent Tool for Genetic Engineering.Frontiers in microbiology · 2020Article
- Protein phosphatases regulate growth, development, cellulases and secondary metabolism in Trichoderma reesei.Scientific reports · 2019Article
- Proteolytic analysis of Trichoderma reesei in celluase-inducing condition reveals a role for trichodermapepsin (TrAsP) in cellulase production.Journal of industrial microbiology & biotechnology · 2019Article
- Challenging the workhorse: Comparative analysis of eukaryotic micro-organisms for expressing monoclonal antibodies.Biotechnology and bioengineering · 2019Article
- Novel genetic tools that enable highly pure protein production in Trichoderma reesei.Scientific reports · 2019Article
- Simultaneous enhancement of the beta-exo synergism and exo-exo synergism in Trichoderma reesei cellulase to increase the cellulose degrading capability.Microbial cell factories · 2019Article
- Fast gene disruption in Trichoderma reesei using in vitro assembled Cas9/gRNA complex.BMC biotechnology · 2019Article
- Enhancement of Cellulase Production inFrontiers in microbiology · 2019Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The filamentous fungus Trichoderma reesei has tremendous capability to secrete proteins. Therefore, it would be an excellent host for producing high levels of therapeutic proteins at low cost. Developing a filamentous fungus to produce sensitive therapeutic proteins requires that protease secretion is drastically reduced. We have identified 13 major secreted proteases that are related to degradation of therapeutic antibodies, interferon alpha 2b, and insulin like growth factor. The major proteases observed were aspartic, glutamic, subtilisin-like, and trypsin-like proteases. The seven most problematic proteases were sequentially removed from a strain to develop it for producing therapeutic proteins. After this the protease activity in the supernatant was dramatically reduced down to 4% of the original level based upon a casein substrate. When antibody was incubated in the six protease deletion strain supernatant, the heavy chain remained fully intact and no degradation products were observed. Interferon alpha 2b and insulin like growth factor were less stable in the same supernatant, but full length proteins remained when incubated overnight, in contrast to the original strain. As additional benefits, the multiple protease deletions have led to faster strain growth and higher levels of total protein in the culture supernatant.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.