First evidence of ovothiol biosynthesis in marine diatoms

Ovothiols are histidine-derived thiols that are receiving a great interest for their biological activities in human model systems. Thanks to the position of the thiol group on the imidazole ring of histidine, these compounds exhibit unusual antioxidant properties. They have been revealing a very promising pharmacological potential due to their anti-proliferative and anti-inflammatory properties, as well as anti-fibrotic activities not always related to their antioxidant power. Ovothiols occur in three differentially methylated forms (A, B and C), isolated from ovary, eggs and biological fluids of many marine invertebrates, mollusks, microalgae, and pathogenic protozoa. These molecules are synthesized by two enzymes: the sulfoxide synthase OvoA and the sulfoxide lyase OvoB. OvoA catalyzes the insertion of the sulfur atom of cysteine on the imidazole ring of histidine, leading to the formation of a sulfoxide intermediate. This is then cleaved by OvoB, giving 5-thiohistidine, finally methylated on the imidazole ring thanks to the methyltransferase domain of OvoA. Recent studies have shown that OvoA homologs are encoded in a wide variety of genomes suggesting that ovothiol biosynthesis is much more widespread in nature than initially thought. Here we have investigated the OvoA occurrence in diatoms, one of the most abundant group of microalgae, dominating marine and freshwater environments. They are considered a very good model system for both biology/photophysiology studies and for biotechnological applications. We have performed comparative sequence and phylogenetic analyses of OvoA from diatoms, highlighting a high degree of conservation of the canonical domain architecture in the analyzed species, as well as a clear clustering of OvoA in the two different morphological groups, i.e. centric and pennate diatoms. The in silico analyses have also revealed that OvoA gene expression is modulated by growth conditions. More importantly, we have characterized the thiol fraction from cultures of the coastal centric diatom Skeletonema marinoi, providing the first evidence of ovothiol B biosynthesis in diatoms.