Plant Molecular Farming – Integration and Exploitation of Side Streams to Achieve Sustainable Biomanufacturing

Abstract

Plants have unique advantages over other systems such as mammalian cells for the production of valuable small molecules and proteins. The benefits cited most often include safety due to the absence of replicating human pathogens, simplicity because sterility is not required during production, scalability due to the potential for open-field cultivation with transgenic plants, and the speed of transient expression potentially providing gram quantities of product in less than 4 weeks. Initially there were also significant drawbacks, such as the need to clarify feed streams with a high particle burden and the large quantities of host cell proteins, but efficient clarification is now readily achieved. Several additional advantages have also emerged reflecting the fact that plants are essentially biodegradable, single-use bioreactors. This article will focus on the exploitation of this concept for the production of biopharmaceutical proteins, thus improving overall process economics. Specifically, we will discuss the single-use properties of plants, the sustainability of the production platform, and the commercial potential of different biomass side streams. We find that incorporating these side streams through rational process integration has the potential to more than double the revenue that can currently be achieved using plant-based production systems.

From stars to stripes: RNA‐directed shaping of plant viral protein templates—structural synthetic virology for smart biohybrid nanostructures

“…All these prerequisites are fulfilled by certain plant viral systems of different shapes, which gain further attractiveness for technical uses through a number of unique attributes delineated above. These include an appropriate robustness despite biodegradability, and sustainable production routes in cell cultures and, to an increasing extent, plant‐based expression systems (Bally et al, ; Buyel, ; Gleba, Klimyuk, & Marillonnet, ; Lomonossoff & D'Aoust, ; Marillonnet, Thoeringer, Kandzia, Klimyuk, & Gleba, ; Marsian & Lomonossoff, ; Rybicki, ; Sack, Hofbauer, Fischer, & Stoger, ; J. Xu, Towler, & Weathers, ). Of primary importance are their repetitive interior and exterior protein surfaces with selectively addressable coupling sites shown to stabilize biomolecules in a striking manner (Poghossian et al, ).…”

High Level Production of Monoclonal Antibodies Using an Optimized Plant Expression System

“…Plant-based biopharmaceuticals can be made in plant cells, tissues, or whole plants that are either stably transformed with the target gene or expressed transiently via agroinfiltration (Buyel, 2019). Since the viability of plant-based expression systems depends strongly on the yield of the target product (Fischer et al, 2015;Sack et al, 2015a), efforts to increase the expression of a desired protein have focused on rigorously optimizing every step in the lifecycle of the target gene product, from delivery of the transgene to the plant cell to the purification of the fully assembled protein.…”

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

“…An important, often insufficiently highlighted feature of N. benthamiana transient expression is its relatively small infrastructure requirements, partially overlapping with those employed in more conventional, medium/high-tech indoors agriculture, such as hydroponics, vertical farming, etc. (Buyel, 2019). In this context, when confronted with the CoVid-19 crisis, we decided to exercise a partial reorientation of the activities in our academic lab, which is equipped with a multipurpose glass greenhouse facility, towards the production of SARS-CoV-2 antigens and antibodies against the virus.…”