Commentary: Extracellular peptidase hunting for improvement of protein production in plant cells and roots

Citation: Kunert KJ and Pillay P (2015) Commentary: Extracellular peptidase hunting for improvement of protein production in plant cells and roots. Despite much recent success in plant-based protein production, key challenges, such as undesired plant proteolytic activities, still severely compromises current recombinant protein production with peptidases affecting protein stability (Pillay et al., 2013). The paper by Lallemand et al. (2015) reporting about identification of extracellular peptidases compromising protein production in plant cells and roots is therefore an excellent contribution to ultimately advance our understanding of peptidase action in plant-based recombinant protein production (Lallemand et al., 2015). Since research has so far not paid a great amount of attention to this problem, a more detailed view, as taken in the paper, is highly beneficial to elucidate such peptidases in the extracellular space. This offers great benefits in terms of protein stability and higher protein production yield. Previous approaches used to address this challenge in plants has for example included peptidase silencing by applying RNA interference technology (Voinnet et al., 2003; Hatsugai et al., 2004) and also co-expressing specific protease inhibitors as " companions " to limit specific protease activities (Goulet et al., 2010, 2012; Pillay et al., 2012). However, silencing a specific peptidase or co-expressing a " companion " protease inhibitor always bears the risk of vital plant metabolic pathways also being affected (Van der Vyver et al., 2003; Senthil-Kumar et al., 2007). This can compromise efficient recombinant protein production in a plant-based system. In addition, work on Arabidopsis, as already done by Lallemand et al. (2015), with its existing wealth of transcriptome and gene data (The_Arabidopsis_Genome_Initiative, 2000) will enable future identification of similar peptidases in other plant species when comparative genomics approaches are applied in combination with Next Generation Sequencing. By investigating two plant species (Arabidopsis thaliana and Nicotiana tabacum); the Lallemand et al. (2015) study particularly unraveled that root-secretion production contained more peptidase activity than, for example, the extracellular medium of cell suspensions. A less proteolytic enriched environment is certainly more favorable for the production of recombinant proteins, especially antibodies. This key finding has, therefore, not only significantly extended our understanding how particular plant species contribute to proteolytic activity and type of peptidase produced but has also contributed to advancing our understanding on how proteases in different plant parts can compromise recombinant protein stability. The study has whereby set a strong working basis for exploring, in the future, proteolytic …