Mycosporine-like amino acids (MAAs) are secondary metabolites of a variety of marine organisms including cyanobacteria and macroalgae. These compounds have strong ultraviolet (UV) absorption maxima between 310 and 362 nm and are biological sunscreens for counteracting the damaging effects of UV radiation in nature. The common MAA shinorine has been used as one key active ingredient of environmentally friendly sunscreen creams. Commercially used shinorine is isolated from one red algae that is generally harvested from the wild. Here, we describe the use of Synechocystis sp. PCC6803 as a host for the heterologous production of shinorine. We mined a shinorine gene cluster from the filamentous cyanobacterium Fischerella sp. PCC9339. When expressing the cluster in Synechocystis sp. PCC6803, we observed the production of shinorine using LC-MS analysis, but its productivity was three times lower than the native producer. Integrated transcriptional and metabolic profiling identified rate-limiting steps in the heterologous production of shinorine. The use of multiple promoters led to a 10-fold increase of its yield to 2.37 ± 0.21 mg/g dry biomass weight, comparable to commercially used shinorine producer. The UV protection of shinorine was further confirmed using the engineered Synechocystis sp. PCC6803. This work was the first time to demonstrate the photosynthetic overproduction of MAA. The results suggest that Synechocystis sp. PCC6803 can have broad applications as the synthetic biology chassis to produce other cyanobacterial natural products, expediting the translation of genomes into chemicals.
Keywords: Synechocystis sp. PCC6803; gene cluster; promoters; shinorine; sunscreen; transcriptional and metabolic profiling.