ArticleJournal of experimental botany2018
Co-expression of a cyclizing asparaginyl endopeptidase enables efficient production of cyclic peptides in planta.
Article in Journal of experimental botany, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
30 citing papers in PubMed, 63 citations in OpenAlex.
- Transcriptome-guided discovery and active-site gatekeeper engineering of a Viola arcuata asparaginyl ligase with superior catalytic performance.The Journal of biological chemistry · 2026Article
- Protein engineering strategies to optimise recombinant product synthesis and accumulation in Nicotiana benthamiana.Plant biotechnology journal · 2026Review
- Advances in cyclotide research: bioactivity to cyclotide-based therapeutics.Molecular diversity · 2025Review
- Review
- Yeast as a tool for exploring disulfide-rich peptides.FEMS yeast research · 2025Review
- Molecular Chimera in Cancer Drug Discovery: Beyond Antibody Therapy, Designing Grafted Stable Peptides Targeting Cancer.International journal of peptide research and therapeutics · 2025Review
- Peptides from plants and microorganisms: a defense strategy for biotic and abiotic stresses.Frontiers in plant science · 2025Review
- New Insights into Involvement of Low Molecular Weight Proteins in Complex Defense Mechanisms in Higher Plants.International journal of molecular sciences · 2024Review
- Hijacking of N-fixing legume albumin-1 genes enables the cyclization and stabilization of defense peptides.Nature communications · 2024Article
- Immunosuppressive Cyclotides: A Promising Approach for Treating Autoimmune Diseases.The protein journal · 2024Review
- Production of Plant Proteins and Peptides with Pharmacological Potential.Advances in biochemical engineering/biotechnology · 2024Review
- Intracellular Application of an Asparaginyl Endopeptidase for Producing Recombinant Head-to-Tail Cyclic Proteins.JACS Au · 2023Article
- Insights into the synthesis strategies of plant-derived cyclotides.Amino acids · 2023Review
- Plant-based production of an orally active cyclotide for the treatment of multiple sclerosis.Transgenic research · 2023Article
- Vacuolar Processing Enzymes in Plant Programmed Cell Death and Autophagy.International journal of molecular sciences · 2023Review
- Rational domestication of a plant-based recombinant expression system expands its biosynthetic range.Journal of experimental botany · 2022Article
- Plant asparaginyl endopeptidases and their structural determinants of function.Biochemical Society transactions · 2021Review
- Yeast-based bioproduction of disulfide-rich peptides and their cyclization via asparaginyl endopeptidases.Nature protocols · 2021Article
- Article
- A bifunctional asparaginyl endopeptidase efficiently catalyzes both cleavage and cyclization of cyclic trypsin inhibitors.Nature communications · 2020Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cyclotides are ultra-stable, backbone-cyclized plant defence peptides that have attracted considerable interest in the pharmaceutical industry. This is due to their range of native bioactivities as well as their ability to stabilize other bioactive peptides within their framework. However, a hindrance to their widespread application is the lack of scalable, cost-effective production strategies. Plant-based production is an attractive, benign option since all biosynthetic steps are performed in planta. Nonetheless, cyclization in non-cyclotide-producing plants is poor. Here, we show that cyclic peptides can be produced efficiently in Nicotiana benthamiana, one of the leading plant-based protein production platforms, by co-expressing cyclotide precursors with asparaginyl endopeptidases that catalyse peptide backbone cyclization. This approach was successful in a range of other plants (tobacco, bush bean, lettuce, and canola), either transiently or stably expressed, and was applicable to both native and engineered cyclic peptides. We also describe the use of the transgenic system to rapidly identify new asparaginyl endopeptidase cyclases and interrogate their substrate sequence requirements. Our results pave the way for exploiting cyclotides for pest protection in transgenic crops as well as large-scale production of cyclic peptide pharmaceuticals in plants.
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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.