Title of Research: Biocatalytic synthesis of natural anti-UV agents
Additional Authors: G. Rubin; G Jiang; Z. Raad; Y Ding.
Exposure to ultraviolet (UV) ray is one important risk factor for skin cancer that can be prevented by the use of sun care products. Synthetic chemical filters (e.g., oxybenzone) are dominant active ingredients in sunscreens. However, recent studies have revealed their accumulation in the human bloodstream to the concentrations much higher than the safety threshold and there are concerns on their negative, lasting environmental impacts. There is thus a significant need for biodegradable and environmentally friendly sunscreen ingredients. Mycosporine-like amino acids (MAAs) are natural UV filters commonly isolated from marine organisms and they are reported to be antioxidants to manage UV-induced oxidative stress, providing a novel two-pronged strategy for skin cancer management. However, previous attempts in synthesizing MAAs via chemical or biosynthetic methods were limited to only a few MAA analogues, constraining their uses for mitigating UV damages. In this work, we identified a nonheme iron(II)- and 2-oxoglutarate-dependent oxygenase (MysH) as a new MAA biosynthetic enzyme. Heterologous expression of refactored MAA gene clusters in E. coli produced three disubstituted MAA analogs porphyra-334, shinorine and mycosporine-glycine-alanine. MysH directly converted the disubstituted MAAs into palythines, which lower the MAA UV absorption maxima from 334 nm to 320 nm and create a functional handle for the mechanistic studies of MAA cellular activities. Biochemical characterization revealed the substrate scope of recombinant MysD and produced four known and two novel disubstituted MAAs. Our study opens new opportunities in the development of next-generation sunscreens for broad range UV-protection, offering a green, nontoxic, and effective strategy to prevent skin cancer.
About the author
Manyun Chen is a 4th year graduate student in Dr. Yousong Ding’s group. Her research direction is to elucidate novel biosynthetic machinery for producing bioactive natural products, e.g. enzymology involved in the biosynthesis of nitropyrroles and mycosporine-like amino acids.