High‐level expression of secreted complex glycosylated recombinant human erythropoietin in the <i>Physcomitrella Δ‐fuc‐t Δ‐xyl‐t</i> mutant

Weise, Andreas; Altmann, Friedrich; Rodriguez‐Franco, Marta; Sjoberg, Eric R.; Bäumer, Wolfgang; Launhardt, Heike; Kietzmann, Manfred; Gorr, Gilbert

doi:10.1111/j.1467-7652.2007.00248.x

Cited by 107 publications

(92 citation statements)

References 48 publications

(55 reference statements)

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“…Due to the fast and precise gene manipulation technique based on homologous recombination in P. patens, the humanization of the moss glycosylation pattern is feasible and glycoengineering in moss plants is already quite advanced (reviewed in Decker et al 2014). To date, several human proteins are produced in moss, e.g., vascular endothelial growth factor (Baur et al 2005), erythropoietin (Weise et al 2007), and human complement factor H (Buettner-Mainik et al 2011). In addition, moss is used as production platform for secondary metabolites such as terpenoids (Bach et al 2014).…”

Section: Extended Moss Resources: Bioinformatics and High Throughput mentioning

confidence: 99%

Can mosses serve as model organisms for forest research?

Müller

Gütle

Jacquot

et al. 2016

Annals of Forest Science

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& Key message Based on their impact on many ecosystems, we review the relevance of mosses in research regarding stress tolerance, metabolism, and cell biology. We introduce the potential use of mosses as complementary model systems in molecular forest research, with an emphasis on the most developed model moss Physcomitrella patens. & Context and aims Mosses are important components of several ecosystems. The moss P. patens is a well-established nonvascular model plant with a high amenability to molecular biology techniques and was designated as a JGI plant flagship genome. In this review, we will provide an introduction to moss research and highlight the characteristics of P. patens and other mosses as a potential complementary model system for forest research. & Methods Starting with an introduction into general moss biology, we summarize the knowledge about moss physiology and differences to seed plants. We provide an overview of the current research areas utilizing mosses, pinpointing potential links to tree biology. To complement literature review, we discuss moss advantages and available resources regarding molecular biology techniques. & Results and conclusion During the last decade, many fundamental processes and cell mechanisms have been studied in mosses and seed plants, increasing our knowledge of plant evolution. Additionally, moss-specific mechanisms of stress tolerance are under investigation to understand their resilience in ecosystems. Thus, using the advantages of model mosses such as P. patens is of high interest for various research approaches, including stress tolerance, organelle biology, cell polarity, and secondary metabolism.

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Section: Extended Moss Resources: Bioinformatics and High Throughput mentioning

confidence: 99%

Can mosses serve as model organisms for forest research?

Müller

Gütle

Jacquot

et al. 2016

Annals of Forest Science

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“…This is especially true for the transgene expression of proteins. Hyp residues, for example, were identified on human erythropoietin (Weise et al, 2007) and IgA1 (Karnoup et al, 2005) recombinantly expressed in Physcomitrella patens and maize (Zea mays), respectively, and Hyplinked O-glycosylation was additionally identified on IgA1, specifically in the Pro/Ser/Thr-rich hinge region where GalNAc O-glycosylation occurs in humans (Karnoup et al, 2005). More recently, Pinkhasov et al (2011) found Hyp formation (Pro-11 or Pro-12) and Hyp substituted with three arabinofuranoside residues in MUC1 TRs transiently expressed in plants.…”

Section: Discussionmentioning

confidence: 99%

Toward Stable Genetic Engineering of Human O-Glycosylation in Plants

et al. 2012

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Glycosylation is the most abundant and complex posttranslational modification to be considered for recombinant production of therapeutic proteins. Mucin-type (N-acetylgalactosamine [GalNAc]-type) O-glycosylation is found in eumetazoan cells but absent in plants and yeast, making these cell types an obvious choice for de novo engineering of this O-glycosylation pathway. We previously showed that transient implementation of O-glycosylation capacity in plants requires introduction of the synthesis of the donor substrate UDP-GalNAc and one or more polypeptide GalNAc-transferases for incorporating GalNAc residues into proteins. Here, we have stably engineered O-glycosylation capacity in two plant cell systems, soil-grown Arabidopsis (Arabidopsis thaliana) and tobacco (Nicotiana tabacum) Bright Yellow-2 suspension culture cells. Efficient GalNAc O-glycosylation of two stably coexpressed substrate O-glycoproteins was obtained, but a high degree of proline hydroxylation and hydroxyproline-linked arabinosides, on a mucin (MUC1)-derived substrate, was also observed. Addition of the prolyl 4-hydroxylase inhibitor 2,2-dipyridyl, however, effectively suppressed proline hydroxylation and arabinosylation of MUC1 in Bright Yellow-2 cells. In summary, stably engineered mammalian type O-glycosylation was established in transgenic plants, demonstrating that plants may serve as host cells for the production of recombinant O-glycoproteins. However, the present stable implementation further strengthens the notion that elimination of endogenous posttranslational modifications may be needed for the production of protein therapeutics.

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“…Разработана методика трансформации P. patens. Первым успешным примером использования этого вида мха в качестве системы экс-прессии рекомбинантных белков стало получение реком-бинантного эритропоэтина человека (Weise et al, 2007). Фирма Grenovation (Германия) разрабатывает технологию наработки биофармацевтических белков на основе P. patens в клеточной суспензионной культуре c применением биореакторов.…”

Section: актуальные технологии генетики и клеточной биологииunclassified

Plant expression systems for production of recombinant pharmaceutically important proteins

Дейнеко¹,

Загорская²

2017

Vestn. VOGiS

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The market of pharmaceutically valuable proteins is the fastest growing segment of the economy. Most biopharmaceuticals have been obtained in mammalian and microorganism cells, but both systems have a num ber of disadvantages. Plant cells combine the advan tages of the eukaryotic system of protein production and the simplicity and cheapness of the bacterial, and the use of plants for the production of recombinant proteins is an economically important and promising direction. The advantage of plant systems is the lower cost of cell cultivation. They are free from unwanted components, such as bacterial endotoxins, hyperglyco sylated proteins produced by yeast, animal and human pathogens in cell cultures of transgenic animals. In ad dition, plants are higher eukaryotes, and therefore full value folding and the formation of multimeric protein complexes occur in their cells, as well as a significant portion of posttranslational modifications similar to those in mammalian cells. The currently developed plant expression systems for recombinant proteins are extremely diverse and number more than 100 different technologies based on different plant species, gene transfer methods, expression strategies, methods for the subsequent extraction of the target protein, etc. This is nuclear and plastid transformation, transient and stable expression during transformation using agro bacterial transport, bombardment or electroporation, cultivation of whole terrestrial or aquatic plants, plant tissues or suspension cell cultures as expression sys tems. The review examines the current state of research in the use of plant expression systems for the produc tion of recombinant proteins for pharmaceuticals. The emphasis was placed on the advantages of plant cell cultures in comparison with other expression systems. Specific examples discuss promising plant systems for the production of recombinant proteins, such as trans plastomic plants, moss and aquatic plant cultures, as well as suspension cultures of cells of higher plants. The current state of the market for recombinant proteins obtained using plant expression systems is considered. The prospects of creating plant ("edible") vaccines based on genetically modified plants are discussed.Key words: expression systems; transgenic plants; bio producers; recombinant proteins; plant vaccines.Рынок фармацевтически ценных белков -наиболее быстро разви вающийся сегмент экономики. Большая часть биофармацевтиков получена в клетках млекопитающих и микроорганизмов, однако обе системы обладают рядом недостатков. Растительные клетки сочетают в себе достоинства эукариотической системы наработки белка и простоту и дешевизну бактериальной. Использование рас тений для получения рекомбинантных белков -экономически зна чимое и перспективное направление. Преимуществом раститель ных систем является более низкая стоимость культивирования клеток. Они свободны от нежелательных компонентов, таких как эндотоксины бактерий, гипергликозилированные белки, продуци руемые дрожжами, патогены животных и человека в кле...

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High‐level expression of secreted complex glycosylated recombinant human erythropoietin in the Physcomitrella Δ‐fuc‐t Δ‐xyl‐t mutant

Cited by 107 publications

References 48 publications

Can mosses serve as model organisms for forest research?

Can mosses serve as model organisms for forest research?

Toward Stable Genetic Engineering of Human O-Glycosylation in Plants

Plant expression systems for production of recombinant pharmaceutically important proteins

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