“Mount Everest of proteins” used by algae to build toxins

While studying how marine algae produce their toxins, scientists discovered the largest protein.

The protein, named PKZILLA-1, is 25% larger than the previous record holder titin. Titin is found in human muscles and can reach 1 micron (or 1 micrometre which is one-thousandth of a millimetre) in length.

PKZILLA-1 and another super-sized protein PKZILLA-2 are described in a paper published in Science.

PKZILLA-1 comes in at 4.7 megadaltons in mass (about 8 billionths of a billionth of a gram) compared to titin which weighs in at 3.7 megadaltons. PKZILLA-2 is 3.2 megadaltons.

“This is the Mount Everest of proteins,” says senior author Bradley Moore, a marine chemist at the University of California San Diego (UCSD). “This expands our sense of what biology is capable of.”

The pair of giant proteins are the enzymes responsible for producing a large, complex molecule called prymnesin – the toxin of the algae Prymnesium parvum which is responsible for massive fish kills.

The researchers mapped out the 239 chemical reactions of the PKZILLA proteins which produce a molecule which “matched perfectly the structure of prymnesin” according to co-first author and UCSD researcher Vikram Shende.

P. parvum is a microalga commonly called golden algae. Each alga is about 10 micrometres in length. The species is found around the world. It was first identified in Texas in 1985. Since then, it is estimated that P. parvum has been responsible for the mass deaths of tens of millions of fish in North America alone.

In 2022, an estimated 1,000 tonnes of fish were lost in the Oder River between Germany and Poland. Scientists believe that P. parvum blooms were responsible.

Blooms of P. parvum see a massive increase in the algae’s population. Its toxins damage the gills of fish and other gill-breathing organisms such as crayfish.

As well as identifying the massive enzymes which produce prymnesin, the team found the large genes which provide the blueprint for making the giant proteins.

This could provide an avenue for tracking and mitigating the effects of harmful algal blooms.

“Monitoring for the genes instead of the toxin could allow us to catch blooms before they start instead of only being able to identify them once the toxins are circulating,” explains co-first author Timothy Fallon, also at UCSD.

Understanding the cellular processes behind the production of PKZILLA-1 and PKZILLA-2 could also benefit in the artificial production of compounds which may be useful in medicine or industry.

“Understanding how nature has evolved its chemical wizardry gives us as scientific practitioners the ability to apply those insights to creating useful products, whether it’s a new anti-cancer drug or a new fabric,” Bradley Moore says.

The team believes their work could aid in finding the genes behind other toxins, such as the ciguatoxin which affects up to 500,000 people a year, allowing for the tracking of these toxins as well.