Abstract:
The use of herbicides over the last 80 years has been a constant driver of global food
production. Specifically, the development of glyphosate-containing herbicides, most
notably Roundup®, has significantly impacted global food security. Glyphosate is a
selective inhibitor of the essential shikimate pathway in plants, bacteria, and fungi. With
increasing critical research into the safety of glyphosate and the emergence of glyphosate-resistant weeds, the search for alternative herbicides has intensified in recent
years. Since herbicides are essential to global food production and security, finding
alternatives to glyphosate is of great importance.
A promising candidate in this search is the bioactive sugar 7-deoxy-sedoheptulose
(7dSh). 7dSh is naturally produced by Synechococcus elongatus and Streptomyces
setonensis. It has been identified as an inhibitor of the shikimate pathway in plants and
cyanobacteria, just like glyphosate. These findings have positioned 7dSh as a promising alternative to glyphosate. However, questions remain about additional working
mechanisms and more economical and efficient methods of 7dSh production.
In this work, Streptomyces setonensis was used to produce 7dSh in 20 L bioreactors,
achieving concentrations of up to 1 g/l. A novel purification protocol was developed that
yields 7dSh with high purity using cost-effective, scalable methods. The development
of an economically scalable production of 7dSh ensures sufficient supply for future
work and provides a basis for the development of potential industrial applications.
A mutant in the highly sensitive strain Trichormus variabilis was found to show no sensitivity to 7dSh. Multi-sequence alignment revealed mutations in genes previously not
linked to 7dSh activity. Although further research is needed, these findings open new
avenues for investigating 7dShs' working mechanisms.
Furthermore, it was shown that 7dSh must be phosphorylated after uptake to be bioactive. Work on chlorotic cells revealed that 7dSh is a potent inhibitor of both glycogen
production and consumption. Furthermore, CO2 flux measurements showed that 7dSh
inhibits CO2 fixation as early as 100 minutes after application. Lastly, 7dSh was shown
to strongly influence glutamate pools in chlorotic and vegetative cells. These findings
cannot be attributed to inhibition of the shikimate pathway and therefore must result
from yet unknown working mechanisms.
Based on these findings, this work suggests that 7dSh is not a selective inhibitor of the
shikimate pathway alone, but rather a potent disruptor of central carbohydrate and nitrogen metabolism.
