A New Pathway
Then in 2007, Albert Eschenmoser, an organic chemist who recently retired from Scripps Research, proposed a new pathway he dubbed the glyoxylate scenario. This involved glyoxylate as an alternative starting point to formaldehyde, and reactions with dihydroxyfumarate (DHF) that Eschenmoser hypothesized could launch a cascade of reactions that would lead to sugars. Glyoxylate was a good starting point because of the possibility that it could be produced by oligomerization of carbon monoxide under potentially prebiotic conditions.
Eschenmoser and Krishnamurthy began developing the experiments to test the hypothesis. At the time, very little was known about relevant reactions involving DHF, and nothing beyond theory about how it reacted with glyoxylate.
The idea that DHF might be involved in a plausible biosynthetic pathway to sugars (via a decarboxylative conversion to glycolaldehyde which aldolizes to sugars) dates back about as far as work on the formose reaction, but the experiments proved otherwise, causing DHF to fall from focus.
"We were thrown a lot of curve balls we had to really think through," said Krisnamurthy of the years he spent working with postdoctoral fellow Vasu Sagi, who is lead author of the new paper. The team's experiments revealed that under the right conditions, DHF and glyoxylate, when in the presence of a few other plausible prebiotic chemicals including formaldehyde, would produce sugars known as ketoses. Ketoses in turn can be converted to critical sugars, including some essential to forming certain amino acids, the DNA and RNA building blocks such as ribose.
In remarkable contrast to the formose reaction, which might only convert a fraction of a percent of its starting materials into ribose, the experiments Sagi slaved over, sometimes monitoring them 24 hours a day, converted vir
|Contact: Mika Ono|
Scripps Research Institute