From cigarettes to high-value products: transforming a traditional crop into biofactory
Plant biotechnology has an emerging role in the production of small-molecule drugs, biologics (vaccines and therapeutics) and diagnostic reagents. It offers a low-cost and scalable alternative to traditional manufacturing platforms based on microbial and animal cells. Moreover, it can address challenges caused by the distribution and storage of drugs, especially in regions of the world with incomplete production chains.
New tobacco plant varieties for drug production
Tobacco plants are highly appreciated as plant biofactories due to their potential as valuable sources of high-value compounds. However, being associated with the manufacture of smoking products, tobacco cultivation is in continuous decline in Europe. The EU-funded Newcotiana project set out to change this perception by developing competitive Nicotiana varieties that can be used for non-smoking products, creating a suitable production platform for the EU bioeconomy and bringing sustainability to a traditional crop. The consortium worked with two plant species, Nicotiana tabacum, the normal cultivated tobacco, and Nicotiana benthamiana, a wild Australian tobacco species. To fully realise the potential of these species as biofactories, scientists had to incorporate specific traits associated with stability, sustainability, and yield of high-value compounds.
Tools for engineering new plant traits
As it was not possible to generate these traits through traditional crop breeding methods, the consortium developed tools to facilitate the accelerated breeding of plant biofactories. “For centuries we have bred our plants using traditional breeding techniques to produce more and better food, or to resist pathogens, but not for better medicine biofactories,” outlines project coordinator Diego Orzaez. New breeding techniques, including genome editing, improved plants for biofactory use in record time. Researchers engineered tobacco plants that do not flower in the field but save the energy to increase their biomass. Moreover, they engineered these plants to avoid unwanted glycosylation or to reduce protease activity, two traits involved in the quality and functionality of the final protein products obtained from the plant. In several cases, plants were engineered to contain a combination of these special traits.
Applications of engineered plants
In the case of the cultivated tobacco species N. tabacum, the consortium enriched the plant composition in added-value compounds with pharmaceutical use. One of these compounds was squalene, a substance currently obtained mainly from unsustainable sources (sharks) and employed as adjuvant in many vaccine formulations. Researchers also produced anatabine, a molecule related to nicotine with anti-inflammatory effects, which is being investigated as a potential treatment for different autoimmune diseases. The engineering of N. benthamiana was slightly different as this plant was already utilised by the industry to produce recombinant proteins used in cosmetics and pharma. Newcotiana partners shared the genome sequence of N. benthamiana to assist teams with the discovery of new bio-pharmaceutical products.
A zero waste biorefinery process
Alongside efforts to improve the market value of these varieties and perhaps enrich them in additional high-end molecules, researchers established a waste zero pilot biorefinery procedure. “The goal is to create a crop and an associated industry that is at least as profitable as the smoking tobacco crop used to be,” emphasises Orzaez. “For this, EU legislation needs to be more flexible and support the engineering of industrial crops.”
Keywords
Newcotiana, plant biotechnology, tobacco plant, Nicotiana tabacum, Nicotiana benthamiana, squalene, anatabine
