A cancer-caused mutation in a protein provides clues to improving the production of a chemical used to make nylon.
Invented in 1935, nylon found its first use replacing silk in stockings. Supplies of nylon dwindled during World War II as the material was funneled towards making rope, parachutes and mosquito netting. Once the war ended, ladies formed long lines – “nylon riots” — at local stores hoping to purchase easy-care nylon stockings once again.
Now nylon is so common, in things from rope to zippers, that it’s hard to imagine supplies were ever low. It’s easy to make too: Mix two particular liquids and nylon strands form where the liquids touch. The synthesis of nylon is a common chemistry demonstration:
Those liquid precursors to nylon, including something called adipic acid, typically come from petroleum processing. Some chemical companies want to create environmentally friendly sources of these chemicals, starting from sugar instead of fossil fuels. These companies hijack and rework the metabolism of bacteria and yeast so the microbes convert sugar into commodity chemicals. Hopefully the final products will be cheaper than their petroleum-derived counterparts, as well as “greener” in terms of releasing less greenhouse gases during production.
One company in California, Verdezyne, has a pilot plant challenging engineered yeast to make adipic acid on a small industrial scale. Meanwhile, researchers look for other microbial metabolic pathways that could be altered to create the 6-carbon adipic acid.
Researchers in Germany cobbled together one potential pathway using proteins from several different bacteria. But this pathway is incomplete: one of the proteins works best using a molecule with five carbon atoms, instead of the six-carbon precursor needed to make adipic acid. Altering the preference of this protein with genetic engineering might make this pathway a viable bio-based route to adipic acid.
Scientists redesign proteins using educated guesses, computer models and time-consuming rounds of evolution. While studying genetic mutations that turn normal cells into cancer, Hai Yan, at Duke University Medical Center, and his colleagues found clues that might help streamline the protein redesign for adipic acid production.
Sometimes those genetic mutations in cancer cells alter metabolic proteins like those scientists tweak for chemical production. In 2008 and 2009, Duke researchers identified an altered protein in cancer cells where the mutation created the reaction needed for the adipic acid pathway. But this cancer protein prefers five-carbon compounds, so the researchers couldn’t insert it directly into the catalytic pathway.
So they identified a structurally similar protein in yeast that preferred six-carbon compounds and mutated it to resemble the change in the cancer cell protein. The altered yeast protein performed the reaction they wanted using a six-carbon molecule, thus completing the biochemical production pathway. The scientists even applied similar logic to redesigning a protein from bacteria, though this protein was less selective than its yeast relative. (Nature Chemical Biology, DOI:10.1038/nchembio.1065)
Using this redesigned protein to make adipic acid in microbes is still a large challenge, as scientists would have to tinker with the microbe’s metabolism to increase adipic acid production. The big lesson from this work is in the design. Cancer-caused mutations that alter a protein’s function, though extremely rare, might be a useful source of information to guide other protein redesigns, the researchers write.
For me, this story is just reminder that science, like many aspects of life, is a creative process. You never know where you’ll find inspiration to solve a problem.