Solving the Mystery of the Billion-Dollar Bond, Double Bond

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John Shanklin, biochemist at Brookhaven National Laboratory, and Ed Whittle, research assistant in Shanklin's lab, with a fatty acid molecule model and plant seeds and casings in the foreground. Courtesy of Brookhaven National Laboratory

John Shanklin, biochemist at Brookhaven National Laboratory, and Ed Whittle, research assistant in Shanklin's lab, with a fatty acid molecule model and plant seeds and casings in the foreground.

Ever since Ian Fleming's hero introduced himself as "Bond, James Bond," bonds have been intertwined with international mystery and adventure.

Recently, researchers in the Office of Science's Brookhaven National Laboratory (BNL) led by John Shanklin have taken a page from Agent 007. With assistance from colleagues in Sweden's Karolinska Institute, they solved a 40-year mystery involving bonds, double bonds. It's a finding that could have billion-dollar implications: One that might leave the world of science stirred, if not shaken.

Specifically, the researchers figured how an enzyme, a protein machine that specializes in driving high-speed chemical reactions, "knows" how to insert double bonds with pinpoint precision in plant fatty acids. According to Dr. Shanklin, plant fatty acids are about a $150 billion business annually. Used in a vast range of products, from polymers to plastics and soaps to industrial feedstocks, fatty acids consist largely of long chains of indistinguishable carbon atoms, with hydrogen atoms stuck to their outside frame.

Inserting a double bond – a process also known as desaturation – essentially means pulling a pair of hydrogen atoms from their carbons. An enzyme, known a desaturase, inserts double bonds at specific sites in the long carbon chain. But how the enzyme finds the right site has long been a mystery, since as Bond once remarked, "All cats are grey in the dark."

The researchers first took a look at two different desaturases, which insert double bonds in different locations. However, the two enzymes looked virtually identical – nothing in their structures showed how they might work differently. So the scientists then used additional crystallography and computer modeling to determine how the two desaturases bind the fatty acids upon which they were working. The fatty acids are actually carried to desaturases by a carrier protein, sort of like a vice that holds the carbon chain in place, so the scientists looked at the entire complex. They found that the carrier proteins of the fatty acids attached to the two desaturases at different orientations, sort of like a vice that holds a 2x4 on a workbench at two different angles.

That clued Dr. Shanklin and his team to look at the blueprints of the enzymes, the sequence of amino acids from which they are built. They did so, and discovered that one of the many differences between the amino acids comprising the sequences of the two enzymes at a place far removed from where the work of desaturation was done was responsible for the different function of the two enzymes. To extend the metaphor, this was a bit like finding the enzymes used the same workbench, but had different doors on their sheds.

But that one difference made all the difference, since the one amino acid repelled part of the carrier protein while the substituted amino acid attracted it, putting the same cut (desaturation) at a totally different location on the fatty acid. (Read more about their work in the Proceedings of the National Academy of Sciences:

Understanding how proteins exert that precise control could show the way to the designer production of plant fatty acids, and, in turn, to new industrial applications and new products.

The possibilities are there, thanks to the resolution of a 40-year mystery, the Office of Science, and, "Bond, Double-Bond."

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Charles Rousseaux is a Senior Writer in the Office of Science.