A cyclotide tide to sweep agriculture?

A cyclotide tide to sweep agriculture?

By Jonathan Ingram, Journal of Experimental Botany

Abundant cyclotide production in plants would be an exciting step forward for agriculture. Such molecular farming could make possible transgenic plants protected by these highly stable defence peptides. Moreover there is the intriguing prospect of cyclotides as medicines in edible plants. A new paper from Simon Poon and co-authors in Journal of Experimental Botany brings these possibilities significantly closer.

Co-expression of a cyclizing asparaginyl endopeptidase enables efficient production of cyclic peptides in planta

Cyclotides hold so much promise. There are two sides to the possibilities, as the key active molecules themselves – plant defence peptides – and as facilitators. As facilitators it is their great stability, conferred to foreign peptides, which is so important. 

But there has been a block: a means of production which can be scaled without exorbitant costs or safety issues. Plant-based production, which has moved on so quickly over recent years, is an attractive option, but so far cyclization has been poor in the right candidates, those plants without a native cyclotide background.

Widely applicable solution

Poon et al. demonstrate that with the introduction of the right asparaginyl endopeptidase, already known to catalyse cyclization, the cyclization issue is greatly improved. This co-expression solution is hugely important, and it isn’t just a one-off. The authors used Nicotiana benthamiana and N. tabacum (the first a leader in plant-based protein production), as well as bush bean (Phaseolus vulgaris), lettuce and canola.

The implications of these findings are thoroughly explored, the authors well aware of a newly opening field and its potential in various applications:

‘The exceptional stability of cyclotides and their reported orally delivered bioactivity from plant material … provides tantalising evidence that bioactive cyclotides could be introduced into edible plants and directly administered as medicines. Successful transient cyclic peptide production in N. benthamiana was transferrable to both bush bean and lettuce as well as stably introduced into canola …

‘The intrinsic insecticidal and nematicidal activity of some cyclotides means that their production in transgenic crops could confer pest protection. Our evidence that cyclotides can be efficiently produced in bush bean, lettuce, tobacco and canola by co-expressing a cyclizing asparaginyl endopeptidase suggests that this approach could be applied to protect agriculturally important crops.’

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Journal of Experimental Botany publishes an exciting mix of research, review and comment on fundamental questions of broad interest in plant science. Regular special issues highlight key areas.