Uncategorized Thursday, 2024/08/29
In a groundbreaking study, a research team from the Scripps Institution of Oceanography at the University of California, San Diego, revealed the secret of how a microalgae called Prymnesium parvum produces complex toxins. During this process, they discovered an unprecedentedly large protein in the field of biology, named PKZILLA-1. This discovery not only broke the record for protein size, but also opened the door to new drug development and material exploration. The relevant research results were published in the Science journal, under the title “Giant polyketide synthase enzymes in the biosynthesis of giant marine polyether toxins “.
One of the leaders of the research team, Professor Bradley Moore, likened PKZILLA-1 to the protein world’s Mount Everest, with a volume 25% larger than the previous record holder, the titin protein in human muscle, and a length of up to an astonishing 1 micrometer. PKZILLA-1 and its smaller colleague PKZILLA-2 together form the key to the production of the deadly toxin prymnesin by the Prymnesium parvum.
The study also discovered abnormally large genes that control the production of these giant proteins, which could greatly improve the monitoring methods for harmful algal blooms caused by Prymnesium parvum. Postdoctoral researcher Timothy Fallon said, “Monitoring genes rather than toxins could allow us to detect them before algal blooms begin, rather than identifying them after toxin diffusion.”
The Prymnesium parvum is a globally distributed unicellular organism, and its overgrowth can lead to fish death because the toxins it secretes can damage fish gills. In 2022, the algae erupted in the Oder River on the border between Poland and Germany, causing the death of 500 to 1000 tons of fish. It poses a threat to aquaculture industries worldwide, from Texas to the Scandinavian Peninsula.
The toxins produced by the Prymnesium parvum belong to a class of compounds called polyketethers, including the major red tide toxin brevetoxin B affecting Florida and ciguatoxin in coral reef fish in the South Pacific and Caribbean. These toxins are one of the largest and most structurally complex molecules in biology, and scientists have long been puzzled by how microorganisms synthesize such massive molecules.
Since 2019, Moore, Fren, and another co-first author, postdoctoral fellow Vikram Shende, have been exploring the toxin production mechanism of Prymnesium parvum from a biochemical and genetic perspective.
In this study, the research team first sequenced the genome of Prymnesium parvum to search for genes related to toxin synthesis. But they were unable to find the answer, which prompted them to switch to a technology specifically designed to discover ultra-long genes for sequencing, ultimately discovering the secret behind the use of giant genes by the Prymnesium parvum to produce giant toxic molecules.
After confirming the PKZILLA-1 and PKZILLA-2 genes, researchers analyzed how these genes guide toxin synthesis. When they pieced together the full picture of the PKZILLA protein, its enormous size was shocking. The mass of PKZILLA-1 protein is as high as 4.7 omen Daltons, while PKZILLA-2 also reaches 3.2 omen Daltons, far exceeding the average mass of ordinary proteins. These proteins are essentially enzymes that can catalyze chemical reactions. Researchers have validated the 239 chemical steps triggered by these two enzymes through calculations, which are completely consistent with the structure of the Prymnesium parvum toxin.
Professor Moore believes that tracking the complex process of toxin production by Prymnesium parvum reveals new strategies for the natural production of complex chemicals. They hope to use this knowledge to synthesize new drugs and materials in the laboratory and open up a new world of chemical research. Genetic monitoring technology will make the monitoring of Prymnesium parvum more efficient and economical, similar to the PCR test widely used during the COVID-19 pandemic. In addition, the research team plans to apply their non-traditional screening techniques to other species that produce polyketide ether toxins, to discover more genes behind the toxins and provide warning mechanisms for harmful algal blooms worldwide, especially those toxins that may affect the health of millions of people, such as ciguatoxin.
This discovery is not only a significant breakthrough in the production mechanism of the toxin from Prymnesium parvum, but also provides a window for the scientific community to gain a deeper understanding of the chemical magic of nature, indicating potential innovative applications in medicine and industry.
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Reference
Timothy R. Fallon et al. Giant polyketide synthase enzymes in the biosynthesis of giant marine polyether toxins. Science, 2024, doi:10.1126/science.ado3290.