Critical Analysis of the Commercial Potential of Plants for the Production of Recombinant Proteins

Stefan Schillberg,Holger Spiegel,Stefan Rasche,Matthias Buntru,Nicole Raven

doi:10.3389/fpls.2019.00720

Abstract

Over the last three decades, the expression of recombinant proteins in plants and plant cells has been promoted as an alternative cost-effective production platform. However, the market is still dominated by prokaryotic and mammalian expression systems, the former offering high production capacity at a low cost, and the latter favored for the production of complex biopharmaceutical products. Although plant systems are now gaining widespread acceptance as a platform for the larger-scale production of recombinant proteins, there is still resistance to commercial uptake. This partly reflects the relatively low yields achieved in plants, as well as inconsistent product quality and difficulties with larger-scale downstream processing. Furthermore, there are only a few cases in which plants have demonstrated economic advantages compared to established and approved commercial processes, so industry is reluctant to switch to plant-based production. Nevertheless, some plant-derived proteins for research or cosmetic/pharmaceutical applications have reached the market, showing that plants can excel as a competitive production platform in some niche areas. Here, we discuss the strengths of plant expression systems for specific applications, but mainly address the bottlenecks that must be overcome before plants can compete with conventional systems, enabling the future commercial utilization of plants for the production of valuable proteins.

Highlights

The function of a protein is determined by the number and sequence of amino acids, which controls the three-dimensional structure of the resulting folded polypeptide
As discussed for the M12 antibody above, cultivation accounts for only 16% of total process costs, whereas downstream processing represents the lion’s share of these costs due to the effort required to extract the protein from the intracellular environment and remove insoluble components of the plant matrix and the many soluble host cell proteins that are released along with the product during homogenization
The low space yield and high cost of downstream processing are major weaknesses limiting the commercial utilization of plant-based production systems

Summary

Introduction

The function of a protein is determined by the number and sequence of amino acids, which controls the three-dimensional structure of the resulting folded polypeptide. Despite the availability of high-performance protein expression hosts, there is a constant demand for improved or completely new systems to reduce manufacturing costs by increasing productivity, quality, and/or yields.

Results

Conclusion