Prospects for the Production of Recombinant Therapeutic Proteins and Peptides in Plants: Special Focus on Angiotensin I-Converting Enzyme Inhibitory (ACEI) Peptides

Abstract

Molecular pharming is a cost-effective, scalable, and safe system to produce high-quality and biologically active recombinant therapeutic proteins. Thus, plants are emerging alternative platform for the production of pharmaceutically relevant proteins such as vaccines, antibodies, antibody derivatives, and some serumderived proteins. Additionally, plants have also been used to produce bioactive and immunogenic peptides. The efficacy, selectivity, specificity, and low toxicity make them particularly well-suited therapeutic agents for various indications, for instance, cardiovascular and infectious diseases, immunological disorders, and cancer. In the broad range of known bioactive peptides, angiotensin I-converting enzyme inhibitory (ACEI) peptides derived from food proteins have attracted particular attention for their ability to prevent hypertension. So far, several ACEI peptides have been identified in food proteins, mainly in milk, eggs, and plants. The industrial production of ACEI peptides is based on enzymatic proteolysis of whole food proteins, which leads to the release of small bioactive peptides with ACE-inhibitory activity. The problems associated to such procedures, namely, cost and loss of functional properties, have demonstrated the need to develop more straightforward methods to produce ACEI peptides. One viable hypothesis, discussed in this chapter, is to genetically engineer crop plants to produce and deliver antihypertensive peptides.

Therapeutic recombinant protein production in plants: Challenges and opportunities

“…A further disadvantage is the need for time‐consuming genetic manipulation procedures requiring backcrosses and plant breeding for the expression of multiple genes and random integration of genes which can adversely affect expression. This could be overcome by novel gene editing techniques such as CRISPR‐Cas9 (Gomes, Oliveira, Vieira, & Duque, ; Jaganathan, Ramasamy, Sellamuthu, Jayabalan, & Venkataraman, ; Miki, Zhang, Zeng, Feng, & Zhu, ). This system, a component of immunity in bacteria, uses clustered regularly interspaced short palindromic repeats (CRISPR) alongside the prokaryotic‐traceable RNA‐guided nuclease Cas9, to precisely edit the genome, and has been applied in both prokaryotes and eukaryotes as a mechanism of genome editing.…”

“…The capacity of plants to carry out glycosylation is an advantage over prokaryotic expression systems; and even in insect and yeast cells, glycosylation capacity is limited (Marsian & Lomonossoff, 2016). Glycoengineering in all of the available systems aims to increase the production of human-like glycosylation TA B L E 1 Advantages and disadvantages of current therapeutic protein expression systems Ghaderi et al, 2012;Gomes et al, 2019;Lagassé et al, 2017;Ma et al, 2003;Verma et al, 1998;Walsh, 2010.…”

“…This is preferable to the current influenza vaccine production system using eggs which ‘does not provide sufficient capacity and adequate speed to satisfy global needs to combat newly emerging strains, seasonal or potentially pandemic' (Shoji et al, ). This provides a significant advantage over conventional methods of responding to rapidly emerging disease strains, as was shown in 2014 when an Ebola treatment was produced at short notice in Nicotiana benthamiana using a transient expression system (Gomes et al, ). This is an opportunity for plant expression systems to excel, producing vaccines quickly in response to emerging threats such as rapidly mutating diseases or bioterror threats.…”

“… Information sourced from Collares, Bongalhardo, Deschamps, & Moreira, ; Demain & Vaishnav, ; Ghaderi et al, ; Gomes et al, ; Lagassé et al, ; Ma et al, ; Verma et al, ; Walsh, . …”

Transforming moss P. patens with lignin peroxidase through heterologous protein expression.

“…It can be scaled to increase the output as well. It is a eukaryote; thus it can complete complex protein folding motifs and post translational modifications (Gomes et al 2019). Bacteria do not have the capability to process this type of gene to become functional.…”