Means to optimize protein expression in transgenic plants

Ullrich, Kristian K.; Hiß, Manuel; Rensing, Stefan A.

doi:10.1016/j.copbio.2014.11.011

Cited by 34 publications

(21 citation statements)

References 74 publications

(60 reference statements)

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“…A global view on protein expression could provide insights into translation regulation mechanisms occurring at the level of initiation and in early stages of elongation. Previous works have revealed the dramatic effect of variable mRNA structural stability on coding portions (Ullrich et al 2015). The stable structure next to the start codon might inhibit initiation and elongation by providing a longer pause during ribosome movement, which consequently, can affect the regulation of co-translational protein folding (Xie 2015).…”

Section: Rna Secondary Structurementioning

confidence: 99%

Optimization of inside and outside factors to improve recombinant protein yield in plant

Habibi

Prado

Pelegrini³

et al. 2017

Plant Cell Tiss Organ Cult

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an improvement of critical features, including transcription, translation and post-translational modifications, in plant cells could make plant systems a safe and economical alternative for biopharmaceutical production. Hence, in this review, the most recent advances influencing the upstream and downstream processes involved in recombinant protein accumulation in plant cells are described. We also discuss how plant systems are becoming the benchmark for the production of several biopharmaceuticals.Keywords Heterologous expression · Host systems · Post-translational modifications · Plant-based pharmaceuticals · Recombinant protein identification and characterization of a promising regulatory pathway for the large-scale production of biopharmaceuticals could strongly contribute to the benefits of this system (Fischer et al. 2012). Molecular pharming technology presents several advantages, including (a) the production of low-cost biomass; (b) end-products lacking human toxicity; (c) the accumulation of complex proteins with correct and proper folding; and (d) straightforward methods for protein purification (Moustafa et al. 2015). Furthermore, molecular pharming offers a flexible, scalable and diverse alternative method for producing new, Abstract The use of plant systems as factories for recombinant protein production became a prominent alternative for pharmaceutical industries due to their high potential for protein accumulation. In the last decades, the application of plants for protein production has gained more attention, as plants represent an economic strategy that leads to high levels of purified and active proteins for the pharmaceutical sector. Currently, FDA approval of the first generation of recombinant proteins produced in carrot cells, taliglucerase alfa, demonstrated that plant cells have a significant capacity to express complex proteins for therapeutic use. Although plant systems still have technical and economic barriers that require improvements in future years, the optimization of upstream and downstream components affecting protein accumulation is considered a key feature in the development of new pharmaceutical proteins. Therefore,

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Section: Rna Secondary Structurementioning

confidence: 99%

Optimization of inside and outside factors to improve recombinant protein yield in plant

Habibi

Prado

Pelegrini³

et al. 2017

Plant Cell Tiss Organ Cult

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“…() and Ullrich et al . ()). Improvements in RNA stability and translation can be achieved by adapting the coding region to the codon usage of plants (Barahimipour et al ., ; Perlak et al ., ; Sharp and Li, ) and integrating the sequence GCT TCC TCC, which encodes Ala‐Ser‐Ser (A), downstream of the initial start codon (Sawant et al ., ).…”

Section: Discussionmentioning

confidence: 99%

“…Because the expected RNA patterns were detected, possible reasons for the low protein yield may be instability of the RNA, low efficiency of translation and protein instability (reviewed by Egelkrout et al (2012) and Ullrich et al (2015)). Improvements in RNA stability and translation can be achieved by adapting the coding region to the codon usage of plants (Barahimipour et al, 2015;Perlak et al, 1991;Sharp and Li, 1987) and integrating the sequence GCT TCC TCC, which encodes Ala-Ser-Ser (A), downstream of the initial start codon (Sawant et al, 2001).…”

Section: Cgpase Production In Plantsmentioning

confidence: 99%

Stable production of cyanophycinase in Nicotiana benthamiana and its functionality to hydrolyse cyanophycin in the murine intestine

Ponndorf

Ehmke

Walliser

et al. 2016

Plant Biotechnology Journal

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SummaryFood supplementation with the conditionally essential amino acid arginine (Arg) has been shown to have nutritional benefits. Degradation of cyanophycin (CGP), a peptide polymer used for nitrogen storage by cyanobacteria, requires cyanophycinase (CGPase) and results in the release of β‐aspartic acid (Asp)‐Arg dipeptides. The simultaneous production of CGP and CGPase in plants could be a convenient source of Arg dipeptides. Different variants of the cphB coding region from Thermosynechococcus elongatus BP‐1 were transiently expressed in Nicotiana benthamiana plants. Translation and enzyme stability were optimized to produce high amounts of active CGPase. Protein stability was increased by the translational fusion of CGPase to the green fluorescent protein (GFP) or to the transit peptide of the small subunit of RuBisCO for peptide production in the chloroplasts. Studies in mice showed that plant‐expressed CGP fed in combination with plant‐made CGPase was hydrolysed in the intestine, and high levels of ß‐Asp‐Arg dipeptides were found in plasma, demonstrating dipeptide absorption. However, the lack of an increase in Asp and Arg or its metabolite ornithine in plasma suggests that Arg from CGP was not bioavailable in this mouse group. Intestinal degradation of CGP by CGPase led to low intestinal CGP content 4 h after consumption, but after ingestion of CGP alone, high CGP concentrations remained in the large intestine; this indicated that intact CGP was transported from the small to the large intestine and that CGP was resistant to colonic microbes.

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“…Stable nuclear transformation (the integration of the target gene into nuclear DNA, followed by obtaining of transgenic plant) is successfully used for the production of antibodies, hormones, peptide inhibitors, and other proteins [17,79]. In particular, this method enables us to accumulate the targeted proteins not only in tissues, but in the dry seeds of cereals, thus avoiding their degradation during long storage [29].…”

Section: Introductionmentioning

confidence: 99%

Chimeric particles of tobacco mosaic virus as a platform for the development of next-generation nanovaccines

2016

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The production of vaccines and other proteins in plants for medical purposes offers a number of advantages over other expression systems. The tobacco mosaic virus (TMV) is an appropriate model for the development of a variety of vectors, including those used for the assembly of chimeric particles carrying heterologous peptides on the surface and inducing an effective immune response. To overcome the problems arising during the assembly of such particles from recombinant subunits of the coat protein, peptide linkers, suppressed stop codons, and proteolytic sites are used. To date, it has been shown that TMV-based nanovaccines provide protection against the viruses of influenza A, foot-and-mouth disease, papilloma, and they are also able to overcome B-cell tolerance for cancer-cell suppression. Genetically modified TMV-based virions can accommodate the ions of various metals and act as affinity agents for protein purification.

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Means to optimize protein expression in transgenic plants

Cited by 34 publications

References 74 publications

Optimization of inside and outside factors to improve recombinant protein yield in plant

Optimization of inside and outside factors to improve recombinant protein yield in plant

Stable production of cyanophycinase in Nicotiana benthamiana and its functionality to hydrolyse cyanophycin in the murine intestine

Chimeric particles of tobacco mosaic virus as a platform for the development of next-generation nanovaccines

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