PKZILLA smashes protein size limits

A new paper in Science details the largest protein discovered to date. The protein, dubbed PKZILLA-1 by the paper’s authors, comes from the haptophyte alga called Prymnesium parvum (2024, DOI: 10.1126/science.ado3290 ). Giant polyketide synthase genes found in P. parvum’s genome encode for a pair of massive proteins. PKZILLA-1 has a mass of 4.7 megadaltons and contains 140 enzyme domains, while its little sibling PKZILLA-2 has a mass of 3.2 megadaltons and contains 99 enzyme domains. Before finding PKZILLA, scientists were already closely familiar with prymnesin-1, an infamous toxin produced by P. parvum . The toxin is responsible for killing hundreds of thousands of fish during algal blooms, most recently in 2022 in Europe’s River Oder . The molecule is also known for its size, with its backbone containing 91 carbons. While prymnesin-1 is well known, it’s been unclear how these huge molecules are synthesized within the cell. The proposed