The polyketide to fatty acid transition in the evolution of animal lipid metabolism

Lipids are crucial to all life, but the biochemical origins of many animal lipids remain unclear. We unveil a previously uncharacterized class of enzymes that is widely occurring in animals, and responsible for producing elaborate lipid- and polyketide-like compounds. These enzymes, the animal FAS-like PKSs (AFPKs), share a common ancestor with the animal fatty acid synthase, which produces the fats needed for animal survival, providing a plausible evolutionary bridge between the drug-like polyketides and the fatty acids. Vertebrates lack AFPKs, but excepting the placental mammals contain PKSs. In contrast, molluscs and arthropods contain abundant AFPKs, correlated with their rich polyketide chemistry. Molluscan AFPKs are associated with a lack of other defenses, consistent with the hypothesis that AFPKs provide a chemical defense for some lineages. By contrast, shelled molluscs (physically defended) generally contain PKSs instead. Arthropods have few PKSs, likely originating in parasites or recent horizontal gene transfer, but their abundant AFPKs potentially contributed to their ecological and evolutionary success. Although animal metabolism is well studied, surprising new metabolic enzyme classes still await discovery and may be unrecognized drivers of hyperdiverse animal radiations including gastropods, beetles and spiders.