Molecular evolution of ovothiol biosynthesis in animal life reveals diversity of the natural antioxidant ovothiols in Cnidaria

Abstract

Sulfoxide synthase OvoA is the key enzyme involved in the biosynthesis of ovothiols (OSHs), secondary metabolites endowed with unique antioxidant properties. Understanding the evolution of such enzymes and the diversity of their metabolites should reveal fundamental mechanisms governing redox signaling and environmental adaptation. "Early-branching" animals such as Cnidaria display unique molecular diversity and symbiotic relationships responsible for the biosynthesis of natural products, however, they have been neglected in previous research on antioxidants and OSHs. In this work, we have integrated genome and transcriptome mining with biochemical analyses to study the evolution and diversification of OSHs biosynthesis in cnidarians. By tracing the history of the ovoA gene, we inferred its loss in the latest common ancestor of Medusozoa, followed by the acquisition of a unique ovoB/ovoA chimeric gene in Hydrozoa, likely through a horizontal gene transfer from dinoflagellate donors. While Anthozoa (corals and anemones), bearing canonical ovoA genes, produced a striking variety of OSHs (A, B, and C), the multifunctional enzyme in Hydrozoa was related to OSH B biosynthesis, as shown in Clytia hemisphaerica. Surprisingly, the ovoA-lacking jellyfish Aurelia aurita and Pelagia noctiluca also displayed OSHs, and we provided evidence of their incorporation from external sources. Finally, transcriptome mining revealed ovoA conserved expression pattern during larval development from Cnidaria to more evolved organisms and its regulation by external stimuli, such as UV exposure. The results of our study shed light on the origin and diversification of OSH biosynthesis in basal animals and highlight the importance of redox-active molecules from ancient metazoans as cnidarians to vertebrates.