Scientists Discovered The Largest Protein Produce Algal Toxins

In their quest to understand how marine algae produce their complex toxins, researchers have identified the largest protein produce algal toxins. This discovery not only sheds light on the biological processes algae use to create these intricate toxins but also reveals new methods for chemical assembly, potentially paving the way for innovative medicines and materials.

Date	August 9, 2024
Source	University of California – San Diego
Summary	The discovery of the biological machinery that algae have evolved to produce their intricate toxins also unveiled new methods for chemical assembly, which could lead to the development of new medicines and materials.

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In their quest to understand how marine algae produce complex toxins, scientists at UC San Diego’s Scripps Institution of Oceanography have identified the largest protein ever recorded in biology.

How Largest Protein Produce Algal Toxins

• The protein, named PKZILLA-1, was found while researchers were studying how the algae species Prymnesium parvum generates its toxin, which is responsible for massive fish die-offs. ‘This is the Mount Everest of proteins,’ said Bradley Moore, a marine chemist with joint appointments at Scripps Oceanography and the Skaggs School of Pharmacy and Pharmaceutical Sciences, and senior author of a new study detailing the findings. ‘This broadens our understanding of what biology can achieve.’
• PKZILLA-1 is 25% larger than titin, the previous record-holder, which is found in human muscles and can reach 1 micron in length (0.0001 centimeter or 0.00004 inch).
• Published in Science and funded by the National Institutes of Health and the National Science Foundation, the study demonstrates that this enormous protein and another large, though not record-breaking, protein—PKZILLA-2—are essential for producing prymnesin, the large, complex molecule that constitutes the algae’s toxin.
• In addition to identifying the giant proteins responsible for prymnesin production, the research also uncovered exceptionally large genes that provide Prymnesium parvum with the instructions for making these proteins.
• Identifying the genes involved in prymnesin production could improve monitoring efforts for harmful algal blooms by enabling water testing to detect the genes rather than the toxins themselves.
• The discovery of PKZILLA-1 and PKZILLA-2 also reveals the algae’s complex cellular process for building these toxins, which have unique and intricate chemical structures. Understanding how these toxins are produced could benefit scientists seeking to synthesize new compounds for medical or industrial use.
• Prymnesium parvum, also known as golden algae, is a single-celled aquatic organism found worldwide in both freshwater and saltwater. Blooms of golden algae are associated with fish die-offs due to the prymnesin toxin, which damages the gills of fish and other aquatic animals.
• In 2022, a golden algae bloom caused the deaths of 500-1,000 tons of fish in the Oder River, which borders Poland and Germany.
• When the researchers completed the assembly of the PKZILLA proteins, they were astonished by their size. The PKZILLA-1 protein has a record-breaking mass of 4.7 megadaltons, while PKZILLA-2 is also very large at 3.2 megadaltons.
• Titin, the previous record-holder, can be up to 3.7 megadaltons—about 90 times larger than a typical protein. After additional tests confirmed that golden algae actually produce these giant proteins in nature, the team set out to determine if the proteins were involved in the production of the prymnesin toxin.
• The PKZILLA proteins are enzymes, meaning they initiate chemical reactions, and the team painstakingly mapped out the 239 chemical reactions driven by the two enzymes using pens and notepads.

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