Big Protein
The largest protein known to science was discovered in Texas, and it plays a role in devastating algae blooms.
By Eva Frederick

In early 2003, rafts of dead fish covered the surface of Lake Granbury in Central Texas — 3 million fish in all. Their bodies formed a shining mat, and the smell attracted birds and other scavengers.
Removing the fish posed a gargantuan task. “They pushed all of those fish into a cove, and they used a front-end loader,” says Greg Southard, a microbiologist at the Texas Parks and Wildlife Department. “From my recollection, they loaded up 18 to 19 dump trucks of dead fish.”
The culprit behind the fish carnage? Golden algae, or Prymnesium parvum. The algae had proliferated in the lake, producing a toxin that is deadly to creatures with gills. Golden algae is found worldwide, and was first detected in Texas in 1985. Last year, Texas water bodies experienced several fish kills due to the algae, which is especially toxic in times of drought when salt and mineral concentrations in the water are high.
Bradley Moore, a biosynthetic chemist at the University of San Diego in California, wanted to learn more about how golden algae's deadly toxin, prymnesin, is made. “We wanted to see if we could understand how nature makes these molecules, and to begin a conversation in the scientific community about how we could monitor for them more precisely, and to think about why these algae make these molecules, and if are there things that we can do to mitigate or forecast them,” Moore says.
In his search, which included a sample from Texas collected by Southard, Moore uncovered something unexpected: the largest protein known to science.

The big protein, called PKZILLA-1, is part of a cellular assembly line that synthesizes the golden algae's toxin. At nearly five megadaltons, the protein is about 25 percent larger than the previous record-holder protein, titin, which is found in muscle cells. “As you can imagine from the name titin, it's big and powerful,” says Moore. “This tiny little algae had something significantly larger than our muscle protein, and it was much, much more complex. That scientifically fascinated us.”
When it came time to name the protein, Moore and colleagues had a sense of humor about it. “We realized that we need to give this protein a special name to be able to stand up to titin, so we called it PKZILLA,” he says. “PK for polyketide… and ZILLA because Godzilla is big, Godzilla is marine, and Godzilla spews toxins. And that's exactly what this protein does. It's big, it's marine, and it makes the toxin prymnesin.”
Understanding the proteins that make golden algae's toxin (and the genes that encode these proteins) has possible implications for the future of fish kill management. Present-day management of golden algae includes regular testing and use of various algicides to contain the algae. Currently, Southard is able to detect the algae by looking at water samples under a microscope and testing for the toxin prymnesin. Being able to test for the genes involved in producing the toxin, instead of the toxin itself, could give authorities some extra lead time to prepare before a bloom happens, treating the water and removing fish when possible.
Now that researchers know the genes involved in making prymnesin, they may even be able to genetically modify golden algae to not produce the toxin. However, there are drawbacks to introducing genetically modified organisms into nature, and it's not clear if a modified strain would be able to outcompete the algae that lives in our lakes and rivers today.
Beyond fisheries management, the discovery of giant protein PKZILLA-1 opens new doors in biologically informed design. “We are beginning to turn more and more to biology to make materials,” Moore says, “and seeing how nature does it in this extraordinary way can teach us something about what we as humans might be able to achieve one day.”

Why does Golden Algae makes its Toxin?
Golden algae grows in two ways: It can photosynthesize, turning sunlight into energy, and it is also a microscopic hunter. “Researchers from Sweden have a video where, kind of like a pack of wolves, little golden algae cells surround a much larger organism, and they're all feeding on it, just basically chomping on the outside of it,” says Southard.
Although it is not scientifically proven, some researchers hypothesize that golden algae may produce their toxin, prymnesin, in order to immobilize other microscopic organisms so they can more easily prey on them. “It just happens that the toxin is toxic to fish and amphibians as well, right?” says Southard. “Non-target species.”