Novel signal peptides for enhancing the secretory production of recombinant proteins in plants

Fusion of novel plant-derived signal peptides enhances the secretion of recombinant proteins into the plant apoplast.

Advantages

  • These newly identified signal peptides (SP) demonstrated more efficient protein secretion than Extensin SP, which is a typical SP enhancing the secretion.
  • These SPs improve the productivity of target proteins.

Technology Overview & Background

Plant production systems has been the most attractive alternatives for producing functional recombinant proteins such as pharmaceuticals, cosmetic ingredients, and industrial enzymes. Besides, various technologies have been developed due to the potential advantage of the low cost of production. Agrobacterium-mediated transient expression (agroinfiltration) is widely used to produce large amounts of protein due to its high expression level. It also has other advantages, such as effectiveness, low-cost production, time saving, and scalability. Compared to other plants, Nicotiana benthamiana has been widely used for recombinant protein production because of its high biomass and susceptibility to a wide range of plant pathogens, the latter of which is useful for introducing foreign genes.
On the other hand, the difficulties in downstream processing of plant-made proteins remain major challenges that limit the industrial or commercial acceptance of plant production systems. The downstream processing such as isolation and purification processes is a major production cost (about 80%). One of the solutions to reduce the cost of these process is through the fusion of SP, guiding target proteins along the secretory pathway to extracellular (or apoplast) space, which might simplify and facilitate the purification process with a larger amount of proteins. Various groups have developed plant-specific signal peptides to improve yields of target protein secretion in plants. Especially, SP derived from N. benthamiana Extensin significantly enhances the secretion of target protein into the apoplast fractions of N. benthamiana leaf tissues.
In this study, we identified novel more efficient secretion-promoting SPs from N. benthamiana than Extensin. These SPs are expected to lead to the efficient production of secreted recombinant proteins.

Patents

  • Patent:Unpublished

Principal Investigator & Academic Institution

Professor Kazuhito Fujiyama (International Center for Biotechnology, Osaka University)

Development Stages & Plans

  • We confirmed the effects of SPs on production of GFP and b-glucocerebrosidase in N. benthamiana. The secretion of recombinant proteins into the apoplast was enhanced by these SPs. Fusions of these SPs exhibited higher secretory efficiencies of recombinant proteins than Extensin.
  • These SPs also exhibited higher secretory efficiencies in the suspension-cultured cells established from N. benthamiana.
  • Next Step:

TECH MANAGE CORP. is looking for a partner company that is interested in this technology.
We can set up a meeting with the PI to introduce the technology and discuss next step.

 

Project No. TT-04561

 

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