Manufactured From Randomness- New Drugs and Plant Growth Regulators
What if we could apply a simple, small molecule to a strawberry plant to trigger flowering and produce fruits? What if we could apply a treatment to something like basil to make it stop flowering so we could enjoy its tasty leaves? What if new environmentally-friendly herbicides could be made that would have no effects on humans or other animals?
Such magical compounds could have tremendous applications both on the farm and in the laboratory. In this week’s Plant Physiology my lab has published an amazingly simple yet extremely powerful new approach to define novel chemistries that affect plant (or other organism) growth — assembled from the randomly scrambled DNA sequence.
How can that possibly work? The best analogy is that we are throwing monkey wrenches into a complicated machine. Most of the time they bounce around and affect nothing. But once in a long while a wrench sticks in some critical gears and brings the machine to a halt. Other times the wrench might short circuit a different process, allowing the machine to run more efficiently.
The first experiments were performed in plants. Plants have many different organs and tissues and change a lot through time. We are more likely to see a conspicuous change compared to tests of bacterial colonies on a petri dish.
A team of scientists made populations of thousands of plants using the model laboratory plant Arabidopsis thaliana. Each plant is slightly different. Each plant contains a tiny stretch of DNA that contains random genetic information. The plant cell translates that information into a small protein with a distinct chemical signature. Every cell creates a molecule that likely never existed before in the universe, and its effects are seen in real time for the first time.
These small random molecules could affect a specific process in the cell, just by chance — monkey wrenches in the machine. They could bind a needed nutrient. They inhibit a key enzyme. They might turn on flowering or prevent salt from being taken up into the plant. Nobody really knows until the plants are examined one by one.
We have already evaluated thousands of plants. We find many that grow slowly; others grow well in conditions where plants don’t survive, like in a high-salt medium. Still others flower early or late. We have found sterile plants, and plants that accumulate lots of pigments.
The central interest is in molecules that are herbicidal — that is, they are lethal to plants because they interfere with some critical biological process. This is exciting because agriculture depends on controlling unwanted species that compete for resources with our food-crops. The new herbicidal molecules may only work on a limited range of plants, killing weeds or invasive species while leaving others unaffected. Peptides are not expected to have any animal toxicity or environmental persistence, so their safety profiles should be extraordinary. Those evaluations are far in the future.
These findings are especially important because new herbicides are rare, and desperately needed. The challenge will now be to find ways to move new compounds into plants when applied from the outside, but that’s a technical step in the hands of other chemistry experts.
The same random information approaches are being used to identify biochemical vulnerabilities in bacteria, primarily in S. aureus, the antibiotic resistant bacteria behind MRSA infections. The approach is also being used to target Liberibacter species, the pathogens that are causing widespread damage to the Florida citrus industry. Could random molecules inform the development of the next generation of antibiotics that target a specific bacterial species, leaving the rest of the microbiome unchanged?
We are now pursuing many research avenues to apply this technology, and it is an exciting time in the Folta Lab.