Rosavin is the characteristic component of L., an important medicinal plant used widely in the world that has been reported to possess multiple biological activities. However, the endangered status of wild Rhodiola has limited the supply of rosavin. In this work, we successfully engineered an strain to efficiently produce rosavin as an alternative production method. Firstly, cinnamate: CoA ligase from , cinnamoyl-CoA reductase from , and uridine diphosphate (UDP)-glycosyltransferase (UGT) from (Bs-YjiC) were selected to improve the titer of rosin in . Subsequently, four UGTs from the UGT91R subfamily were identified to catalyze the formation of rosavin from rosin, with SlUGT91R1 from showing the highest activity level. Secondly, production of rosavin was achieved for the first time in by incorporating the SlUGT91R1 and UDP-arabinose pathway, including UDP-glucose dehydrogenase, UDP-xylose synthase, and UDP-xylose 4-epimerase, into the rosin-producing stain, and the titer reached 430.5 ± 91.4 mg/L. Thirdly, a two-step pathway derived from -arabinose, composed of -arabinokinase and UDP-sugar pyrophosphorylase, was developed in to further optimize the supply of the precursor UDP-arabinose. Furthermore, 1203.7 ± 32.1 mg/L of rosavin was produced from -glucose and -arabinose using shake-flask fermentation. Finally, the production of rosavin reached 7539.1 ± 228.7 mg/L by fed-batch fermentation in a 5-L bioreactor. Thus, the microbe-based production of rosavin shows great potential for commercialization. This work provides an effective strategy for the biosynthesis of other valuable natural products with arabinose-containing units from -glucose and -arabinose.

中文翻译：

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工程大肠杆菌中D-葡萄糖和L-阿拉伯糖高水平生产红景天特征成分松香素


Rosavin是L.的特征成分，L.是一种在世界范围内广泛使用的重要药用植物，据报道具有多种生物活性。然而，野生红景天的濒危状况限制了松香素的供应。在这项工作中，我们成功地设计了一种菌株，可以有效生产松香素作为替代生产方法。首先，选择来自 的肉桂酸：CoA 连接酶、来自 的肉桂酰辅酶A还原酶和来自（Bs-YjiC）的尿苷二磷酸（UDP）-糖基转移酶（UGT）来提高 中松香的效价。随后，鉴定出 UGT91R 亚家族的 4 个 UGT 能够催化松香形成松香素，其中 SlUGT91R1 显示出最高的活性水平。其次，通过将SlUGT91R1和UDP-阿拉伯糖途径（包括UDP-葡萄糖脱氢酶、UDP-木糖合酶和UDP-木糖4-差向异构酶）整合到松香生产染料中，首次实现了松香素的生产，并且滴度达到430.5±91.4mg/L。第三，开发了由α-阿拉伯糖衍生的由α-阿拉伯激酶和UDP-糖焦磷酸化酶组成的两步​​途径，以进一步优化前体UDP-阿拉伯糖的供应。此外，通过摇瓶发酵，由α-葡萄糖和-阿拉伯糖生产了1203.7 ± 32.1 mg/L 的rosavin。最终，通过在5L生物反应器中补料分批发酵，松香素的产量达到7539.1±228.7mg/L。因此，基于微生物的松香生产显示出巨大的商业化潜力。这项工作为利用α-葡萄糖和α-阿拉伯糖的含阿拉伯糖单元生物合成其他有价值的天然产物提供了有效的策略。