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.

中文翻译：

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利用工程蓝细菌光合作用生产防晒霜

霉菌素样氨基酸（MAAs）是包括蓝细菌和大型藻类在内的各种海洋生物的次生代谢产物。这些化合物在310至362 nm之间具有很强的紫外线（UV）吸收最大值，是生物防晒剂，可抵消自然界中UV辐射的破坏作用。常见的MAA紫精碱已用作环保防晒霜的一种关键活性成分。商业上使用的紫碱碱是从一种通常从野外收获的红藻中分离出来的。在这里，我们描述了集胞藻的使用。PCC6803作为shinorine异源生产的宿主。我们从丝状蓝藻Fischerella sp。中提取了shinorine基因簇。PCC9339。在表达集群时集胞藻 PCC6803，我们使用LC-MS分析观察到了紫罗兰碱的生产，但其生产率比本地生产商低三倍。整合的转录和代谢谱分析确定了shinorine异源生产中的限速步骤。与商业上使用的紫罗兰碱生产商相比，使用多种启动子可将其产量提高10倍，至2.37±0.21 mg / g干生物质重量。使用工程化的集胞藻（Synechocystis sp。）进一步证实了shinorine的紫外线防护。PCC6803。这项工作是第一次证明MAA的光合作用过量生产。结果表明，集胞藻sp。PCC6803作为合成生物学底盘可以广泛地应用于生产其他蓝藻天然产物，从而加速了基因组向化学物质的转化。