Planta Med 2015; 81 - PN6
DOI: 10.1055/s-0035-1556332

De novo synthesis of a vertebrate sunscreen compound

AR Osborn 1, KH Almabruk 1, G Holzwarth 2, S Asamizu 1, J LaDu 3, KM Kean 4, PA Karplus 4, RL Tanguay 3, AT Bakalinsky 2, T Mahmud 1
  • 1Department of Pharmaceutical Sciences
  • 2Department of Food Science and Technology
  • 3Department of Environmental and Molecular Toxicology
  • 4Department of Biochemistry and Biophysics, Oregon State University, Corvallis, OR 97331, USA

Current paradigms suggest that gadusol, a sunscreen and antioxidant found in fish, is derived from 4-deoxygadusol, a precursor of mycosporine-like amino acids produced by cyanobacteria, fungi, algae, and marine invertebrates. The accumulation of these compounds in marine animals has been proposed to be of dietary or symbiont origin. Here, we report that gadusol is synthesized de novo in zebrafish (Danio rerio) from a pentose phosphate pathway intermediate, sedoheptulose 7-phosphate, by a novel two-enzyme system, a 2-epi-5-epi-valiolone synthase (EEVS) and a methyltransferase-oxidoreductase (MT-Ox). Heterologous expression of the fish genes in engineered yeast resulted in the production of gadusol in yeast. The product suppresses the UVB-sensitivity of a rad1Δ mutant of Saccharomyces cerevisiae, confirming the UVB-protective activity of gadusol.