Marine algae use massive enzymes of unprecedented size to biosynthesize fish-killing toxins

Marine algae Prymnesium parvum use massive enzymes dubbed PKZILLAs – some of the largest proteins ever to be identified in nature – to make large and complex prymnesin neurotoxins responsible for mass fish kills during harmful algal blooms worldwide, researchers report. “The discovery and initial characterization of the prymnesin PKZILLA gigasynthases now elucidates the long-standing question about how microalgae biosynthesize their giant polyketide polyether molecules,” write the authors. It also expands expectations of genetic and enzymatic size limits in biology. Many marine microbes produce exotic organic molecules with varied biological functions. Some microalgae, like P.  parvum, are known for producing some of the largest nonpolymeric carbon chain molecules in nature, including polyketide polyether biotoxins. During harmful algal blooms, neurotoxic prymnesins compounds are notorious for causing environmental damage, including massive environmental fish kills. However, despite decades of extensive research, how these microalgae produce such large and complex compounds is poorly understood. Using a customized gene annotation strategy, Timothy Fallon and colleagues discovered genes in P. parvum, which they named PKZILLAs (PKZILLA-1 and PKZILLA-2), that are involved in the production of polyketide synthase (PKS) enzymes. Notably, Fallon et al. found that these enzymes were massive, with PKZILLA-1 being one of the largest proteins ever identified at 4.7 megadaltons and containing 140 enzyme domains. Although slightly smaller, PKZILLA-2 is 3.2 megadaltons with 99 enzyme domains. According to the findings, these massive PKS gigasynthases are responsible for the biosynthesis of the 90-carbon backbone of prymnesin toxins. The authors also characterized a variant, PKZILLA-B1, which produces a shorter version of these toxins.

For reporters interested in other research that challenges prevailing views of the size limits of biological entities, a 2022 Science Research Article reported discovering discovering a bacterium so large that it can be seen by the naked eye.