Lipoxygenase AsLOX2 Catalyzes the Gateway Oxygenation Step in the Biosynthesis of the UV-Absorbing Oxylipin Saclipin in the Edible Cyanobacterium Aphanothece sacrum

Abstract Saclipins A and B are ultraviolet (UV)-absorbing oxylipin metabolites isolated from the freshwater cyanobacterium Aphanothece sacrum (Suizenji-nori) and represent promising candidates as naturally derived UV-filter compounds. Here, we identified lipoxygenase AsLOX2 as a key enzyme initiating saclipin biosynthesis and establish a practical route for saclipin production from α-linolenic acid (ALA). Using ALA as a substrate, AsLOX2 catalyzed oxygenation at the C9 and C16 positions, generating a hydroperoxide intermediate associated with saclipin biosynthesis. Although the endogenous enzymatic step converting this intermediate into saclipin remains unresolved, we demonstrate that the AsLOX2-derived intermediate can be chemically converted into saclipins via SnCl2 reduction followed by MnO2 oxidation. These findings define the gateway reaction in saclipin biosynthesis and provide an experimental route for saclipin production, facilitating the future development of naturally derived UV-protective materials.