Hundreds of naturally occurring specialty fatty acids (building blocks of oils) have potential for use as raw materials for making lubricants, plastics, pharmaceuticals, and more—if they could be produced at large scale by crop plants. But attempts to put genes for making these specialty building blocks into crops have had the opposite effect: Seeds from plants with genes added to make specialty fatty acids accumulated dramatically less oil. No one knew why.
Now two teams of biochemists working on separate aspects of oil synthesis at the U.S. Department of Energy's Brookhaven National Laboratory have converged to discover the mechanism behind the oil-production slowdown. As described in the journal Plant Physiology, they crossbred model plants and conducted detailed biochemical-genetic analyses to demonstrate a strategy for reversing the roadblock and ramping up production. The work paves the way for making at least one industrially important specialty fatty acid in plants—and may work for many others.
"Since scientists discovered the genes responsible for making specialty
fatty acids several decades ago, we've dreamed of putting them into crop plants to make abundant renewable sources of desired fatty acids," said John Shanklin, chair of Brookhaven Lab's biology department, who oversaw the project. "But we've been stymied from using them because we didn't know why they dramatically slow fatty acid and oil synthesis. A number of research groups have been trying to figure out why this happens. We have now nailed down the mechanism and opened up the possibility of achieving that dream."
Two projects converge
This study grew out of two separate projects in Shanklin's biochemistry lab. One, led by Xiao-Hong Yu and Yuanheng Cai, was focused on the challenges associated with specialized fatty acid production in plants. The other, led by Jantana Keereetaweep, was deciphering details of the biochemical feedback loop plants use to regulate ordinary fatty acid and oil production.
Through that second project, the team recently characterized a mechanism by which plants down-regulate oil synthesis when levels of a plant's regular (endogenous) fatty acids get too high.
"This system operates like a thermostat," Shanklin explained. "When heat gets above its set point, the furnace turns off."
In the case of plant oils, the key machinery that controls production is an enzyme called ACCase. It has four parts, or subunits—you can think of them as gears. As long as endogenous fatty acids are below a certain level, the four "gears" mesh and the machine cranks out fatty acids for oil production. But feeding plants additional endogenous fatty acids triggers a substitution in the machinery. One of the ACCase subunits gets replaced by a version that isn't functional. "It's like a gear with no teeth," Shanklin said. That toothless gear (known as BADC) slows the fatty acid-producing machinery until endogenous fatty acid levels fall.
In contrast, the shutdown mechanism triggered by the specialty fatty acids (ones being produced by genes artificially added to the plant) kicks in when even small amounts of the "foreign" fatty acids are present, and endogenous fatty acids aren't in excess. "Because of this, they appeared to be two separate processes," Shanklin said.
But as the two teams discussed their projects, they began to wonder if the specialty fatty acids were triggering the same off switch triggered by high levels of ordinary fatty acids. "Imagine working in the same lab on different projects and in a lab meeting one day, you look at each other and ask, "Is it possible we're working on the same thing?'" Shanklin said.
This idea provided a way for the teams to combine efforts on a new experiment.
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