Shinorine

Mycosporine-like amino acids (MAAs), microbial secondary metabolites with ultraviolet (UV) absorption properties, are promising natural sunscreen materials. Due to the low efficiency of extracting MAAs from natural producers, production in heterologous hosts has recently received attention. Shinorine is a well characterized MAA with strong UV-A absorption property. Previous, we developed Saccharomyces cerevisiae strain producing shinorine by introducing four shinorine biosynthetic genes from cyanobacterium Nostoc punctiforme. Shinorine is produced from sedoheptulose 7-phosphate (S7P), an intermediate in the pentose phosphate pathway. Shinorine production was greatly improved by using xylose as a co-substrate, which can increase the S7P pool. However, due to a limited xylose-utilizing capacity of the engineered strain, glucose was used as a co-substrate to support cell growth. In this study, we further improved shinorine production by attenuating glucose catabolism via glycolysis, which can redirect the carbon flux from glucose to the pentose phosphate pathway favoring shinorine production. Of the strategies we examined to reduce glycolytic flux, deletion of HXK2, encoding hexokinase, was most effective in increasing shinorine production. Furthermore, by additional expression of Ava3858 from Anabaena variabilis, encoding a rate-limiting enzyme 2-demethyl 4-deoxygadusol synthase, 68.4 mg/L of shinorine was produced in an optimized medium containing 14 g/L glucose and 6 g/L xylose, achieving a 2.2-fold increase compared with the previous strain.

Mycosporine-like amino acids (MAAs) have been used in cosmetics and pharmaceuticals. The purpose of this work was to develop yeast strains for sustainable and economical production of MAAs, especially shinorine. First, genes involved in MAA biosynthetic pathway from Actinosynnema mirum were introduced into Saccharomyces cerevisiae for heterologous shinorine production. Second, combinatorial expression of wild and mutant xylose reductase was adopted in the engineered S. cerevisiae to facilitate xylose utilization in the pentose phosphate pathway. Finally, the accumulation of sedoheptulose 7-phosphate (S7P) was attempted by deleting transaldolase-encoding TAL1 in the pentose phosphate pathway to increase carbon flux toward shinorine production. In fed-batch fermentation, the engineered strain (DXdT-M) produced 751 mg/L shinorine in 71 h. Ultimately, 54 mg/L MAAs was produced by DXdT-M from rice straw hydrolysate. The results suggest that shinorine production by S. cerevisiae might be a promising process for sustainable production and industrial applications.

Mycosporine-like amino acids (MAAs) such as shinorine and porphyra-334 from Porphyra spp. are bioactive compounds with strong photoprotective and antioxidant properties. In this study, the anti-adipogenic effect of shinorine and porphyra-334 was examined in vitro utilizing 3T3-L1 preadipocytes. Shinorine and porphyra-334 were extracted from laver (Porphyra dentata) 50% methanolic (MeOH) extract of and their structures were elucidated by MS and NMR spectroscopy. Both compounds had no cytotoxic effect in 3T3-L1 cells (< 200 μg/mL) and inhibited the accumulation of lipid droplets in 3T3-L1 mature adipocytes in a dose-dependent manner (0.1 and 1.0 μM). Interestingly, both compounds had also significantly reduced the expression of adipogenic-related genes such as peroxisome proliferator-activated receptor γ2 (PPARγ2), CCAAT/enhancer-binding protein α (C/EBPα), adiponectin, and leptin in 3T3-L1 cells. The findings suggest that shinorine and porphyra-334 have the potential to inhibit adipogenesis in 3T3-L1 preadipocytes.