Development of Systems for the Production of Plant-Derived Biopharmaceuticals

Moon, Ki-Beom; Park, Ji-Sun; Park, Y I; Song, In Ja; Lee, Hyo Jun; Cho, Hye Sun; Jeon, Jae Heung; Kim, Hyun Soon

doi:10.3390/plants9010030

Cited by 83 publications

(65 citation statements)

References 115 publications

(127 reference statements)

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“…Lastly, we evaluated if event stacking can enhance the 5% of TSP or 82.5 mg/kg) can be successfully produced in sugarcane culms using the combinatorial promoter and event stacking strategies. Previous studies utilized multiple plant species, tissue types, and expression systems for recombinant protein production 40,41 . Majority of them used transient Agrobacterium-and viral vector-based approaches in Nicotiana benthamiana or N. tabacum [42][43][44][45][46] .…”

Section: Resultsmentioning

confidence: 99%

Unprecedented enhancement of recombinant protein production in sugarcane culms using a combinatorial promoter stacking system

Damaj¹,

Jifon

Woodard

et al. 2020

Sci Rep

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Plants represent a safe and cost-effective platform for producing high-value proteins with pharmaceutical properties; however, the ability to accumulate these in commercially viable quantities is challenging. Ideal crops to serve as biofactories would include low-input, fast-growing, highbiomass species such as sugarcane. The objective of this study was to develop an efficient expression system to enable large-scale production of high-value recombinant proteins in sugarcane culms. Bovine lysozyme (BvLz) is a potent broad-spectrum antimicrobial enzyme used in the food, cosmetics and agricultural industries. Here, we report a novel strategy to achieve high-level expression of recombinant proteins using a combinatorial stacked promoter system. We demonstrate this by co-expressing BvLz under the control of multiple constitutive and culm-regulated promoters on separate expression vectors and combinatorial plant transformation. BvLz accumulation reached 1.4% of total soluble protein (TSP) (10.0 mg BvLz/kg culm mass) in stacked multiple promoter:BvLz lines, compared to 0.07% of TSP (0.56 mg/kg) in single promoter:BvLz lines. BvLz accumulation was further boosted to 11.5% of TSP (82.5 mg/kg) through event stacking by re-transforming the stacked promoter:BvLz lines with additional BvLz expression vectors. The protein accumulation achieved with the combinatorial promoter stacking expression system was stable in multiple vegetative propagations, demonstrating the feasibility of using sugarcane as a biofactory for producing highvalue proteins and bioproducts. Recombinant proteins are currently being produced in cultured cell-based systems in mammals, microbes (bacteria and yeast), insects and plants, as well as in transgenic animals (reviewed by Demain and Vaishnav) 1. Transgenic plants constitute an attractive system for expression and production of a variety of proteins and biomolecules due to their efficient eukaryotic protein synthesis, high scalability, relatively low production costs and environmental footprint 2-4. However, selecting suitable hosts and expression vectors are key considerations since protein accumulation is determined by expression levels. Important factors to consider when selecting a plant-based production platform include biomass yield per hectare, recombinant protein yield per unit biomass, ease of transformation, scalability and safety 5. Sugarcane

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Section: Resultsmentioning

confidence: 99%

Unprecedented enhancement of recombinant protein production in sugarcane culms using a combinatorial promoter stacking system

Damaj¹,

Jifon

Woodard

et al. 2020

Sci Rep

View full text Add to dashboard Cite

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“…Recombinant protein production in plants is a technologically mature bioengineering discipline, with most current plant-based bioproduction platforms making use of non-food crops, mainly the Nicotiana species tabacum and N. benthamiana as biomanufacturing chassis (Moon et al, 2019; Capell et al, 2020). N. benthamiana is most frequently used in association with Agrobacterium-mediated transient expression, also known as agroinfiltration, a technology that dramatically reduces the time required for product development.…”

Section: Introductionmentioning

confidence: 99%

Pilot production of SARS-CoV-2 related proteins in plants: a proof of concept for rapid repurposing of indoors farms into biomanufacturing facilities

Diego-Martin

González

Vázquez‐Vilar

et al. 2020

Preprint

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The current CoVid-19 crisis is revealing the strengths and the weaknesses of the world's capacity to respond to a global health crisis. A critical weakness has resulted from the excessive centralization of the current biomanufacturing capacities, a matter of great concern, if not a source of nationalistic tensions. On the positive side, scientific data and information have been shared at an unprecedented speed fuelled by the preprint phenomena, and this has considerably strengthened our ability to develop new technology-based solutions. In this work we explore how, in a context of rapid exchange of scientific information, plant biofactories can serve as a rapid and easily adaptable solution for local manufacturing of bioreagents, more specifically recombinant antibodies. For this purpose, we tested our ability to produce, in the framework of an academic lab and in a matter of weeks, milligram amounts of six different recombinant monoclonal antibodies against SARS-CoV-2 in Nicotiana benthamiana. For the design of the antibodies we took advantage, among other data sources, of the DNA sequence information made rapidly available by other groups in preprint publications. mAbs were all engineered as single-chain fragments fused to a human gamma Fc and transiently expressed using a viral vector. In parallel, we also produced the recombinant SARS-CoV-2 N protein and its Receptor Binding Domain (RBD) in planta and used them to test the binding specificity of the recombinant mAbs. Finally, for two of the antibodies we assayed a simple scale-up production protocol based on the extraction of apoplastic fluid. Our results indicate that gram amounts of anti-SARS-CoV-2 antibodies could be easily produced in little more than 6 weeks in repurposed greenhouses with little infrastructure requirements using N. benthamiana as production platform. Similar procedures could be easily deployed to produce diagnostic reagents and, eventually, could be adapted for rapid therapeutic responses.

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“…In this perspective, the output of FoodMine constitutes a valuable starting point for the creation of standards necessary for targeted metabolomics, helping identify and quantify the variability of these chemical compounds in food. 30,31 Our next goal is to expand the data collection to multiple staple ingredients. We are prioritizing our search according to the consumption and production statistics available in national and international surveys like NHANES 32 and FAOSTAT 33 , aiming to target foods that would help drastically improve the chemical coverage of our diet, and benefit health studies.…”

Section: Discussionmentioning

confidence: 99%

Exploring Food Contents in Scientific Literature with FoodMine

Hooton

Menichetti

Barabási

2019

Preprint

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Thanks to the many chemical and nutritional components it carries, diet critically affects human health. However, the currently available comprehensive databases on food composition cover only 188 nutritional components that are essential for our health, a tiny fraction of the total number of chemicals present in our food. Indeed, thousands of other molecules, many of which have well documented health implications, remain untracked. To explore the body of knowledge available on food composition, we built FoodMine, an algorithm that uses natural language processing to identify papers from PubMed that potentially report on the chemical composition of garlic and cocoa. After extracting from each paper information on the reported quantities of chemicals, we find that the scientific literature carries extensive information on the detailed chemical components of food that is currently not integrated in databases. Finally, we use unsupervised machine learning to create chemical embeddings, finding that the chemicals identified by FoodMine tend to have direct health relevance, reflecting the scientific community's focus on health-related chemicals in our food.

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Development of Systems for the Production of Plant-Derived Biopharmaceuticals

Cited by 83 publications

References 115 publications

Unprecedented enhancement of recombinant protein production in sugarcane culms using a combinatorial promoter stacking system

Unprecedented enhancement of recombinant protein production in sugarcane culms using a combinatorial promoter stacking system

Pilot production of SARS-CoV-2 related proteins in plants: a proof of concept for rapid repurposing of indoors farms into biomanufacturing facilities

Exploring Food Contents in Scientific Literature with FoodMine

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