Convergent evolution enables eicosanoid precursor biosynthesis by ‘first’ fatty acyl desaturases in insects

Eicosanoids are vital signaling molecules in animals. Yet, the enzymes biosynthesizing their polyunsaturated fatty acid (FA) precursors in insects remain largely unknown. Canonical ‘front-end’ FADS-like desaturases, which mediate this process in most animals, are generally absent from insect genomes, leaving a major gap in insect lipid metabolism. Here, we demonstrate that members of the SCD-like FAD-B subfamily have acquired Δ5 regiospecificity and structural capacity to accept long-chain and polyunsaturated substrates. Phylogenomic analysis, AlphaFold structural modelling, and yeast functional expression revealed that FAD-B paralogs from termites and four other insect orders produce 5 Z -unsaturated FAs across a broad substrate range. Two termite paralogs additionally desaturate eicosanoid precursors, including sciadonic and arachidonic acid precursors. FA profiling of termite tissues, combined with the absence of Δ6 pathway intermediates, supports a noncanonical route to arachidonic acid. These findings reveal convergent evolution of ‘front-end’-like activity within the SCD-like family, expanding the catalytic repertoire of insect desaturases.