Scientists at the University of California San Diego’s Scripps Institution of Oceanography have identified the largest protein ever discovered. The protein in question, called PKZILLA-1, was discovered while scientists were investigating how marine algae produce their potent toxins.

This discovery not only reveals new aspects of biology but also opens doors to innovative medical and industrial applications.

A Giant Among Proteins

PKZILLA-1, the newly discovered protein, is 25% larger than titin, the previous record holder found in human muscles. This discovery was made in Prymnesium parvum, algae responsible for massive fish kills in both fresh and saltwater due to the toxin prymnesin. For instance, in 2022, a golden algae bloom killed 500-1,000 tons of fish in the Oder River adjoining Poland and Germany.

The toxin-producing machinery of this single-celled organism has puzzled scientists for years. Now, armed with the identification of PKZILLA-1, scientists have crucial insights into how such complex chemicals are made and can design countermeasures.

Bradley Moore, a marine chemist at Scripps and senior author of the study, described PKZILLA-1 as “the Mount Everest of proteins.” The protein’s mass of 4.7 megadaltons overshadows titin’s 3.7 megadaltons, setting a new record in biological science. One dalton is roughly equivalent to the mass of a single hydrogen atom, which is the lightest and simplest atom. This means that PKZILLA-1 is equal to about 4.7 million hydrogen atoms. Of course, this is still incredibly tiny by our standards but huge in the microscopic world.

A Closer Look

Moore and colleagues first sequenced the entire genome of the species, before zooming in on genes that may be involved in producing prymnesin. This proved more challenging than they thought. But, eventually, after using a method called genetic sleuthing, the researchers were able to find the genes responsible for coding the toxin-producing protein.

This is how they singled out PKZILLA-1 and PKZILLA-2 (another key protein involved in prymnesin production though not nearly as big as the former). By calibrating instruments to look for the genes that produce these enzymes, researchers believe it may be possible to detect algal blooms before toxins are released into the environment, enhancing early warning systems.

“Monitoring for the genes instead of the toxin could allow us to catch blooms before they start,” said Timothy Fallon, a postdoctoral researcher and co-author of the study. This approach could mirror the PCR tests widely used during the COVID-19 pandemic, offering a cost-effective and timely method to prevent ecological disasters.

Beyond environmental applications, the study’s findings could pave the way for developing new drugs and materials. By understanding the intricate process through which nature creates such complex molecules, scientists can replicate or even modify these processes in the laboratory. Moore suggests that this knowledge could lead to breakthroughs in creating new anti-cancer drugs or advanced materials.

The findings appeared in the journal Science.