5-Methyluridine (5-MU) is a prominent intermediate for industrial synthesis of several antiviral-drugs, however, its availability over the past decades has overwhelmingly relied on chemical and enzymatic strategies. Here, we have realized efficient production of 5-MU in for the first time, a designer artificial pathway consisting of a two-enzyme cascade (UMP 5-methylase and phosphatase). More importantly, we have engineered the cell factory to boost 5-MU production by systematic evaluation of multiple strategies, and as a proof of concept, we have further developed an antibiotic-free fermentation strategy to realize 5-MU production (10.71 g/L) in MB229 (a strain). Remarkably, we have also established a versatile and robust platform with exploitation of the engineered for efficient production of diversified UMP-derived chemicals. This study paves the way for future engineering of as a synthetic biology platform for acceleratively accessing UMP-derived chemical diversities.

中文翻译：

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开发大肠杆菌平台以高效生产 UMP 衍生化学品


5-甲基尿苷 (5-MU) 是工业合成多种抗病毒药物的重要中间体，但在过去几十年中，其可用性很大程度上依赖于化学和酶促策略。在这里，我们首次实现了 5-MU 的高效生产，这是一种由双酶级联（UMP 5-甲基化酶和磷酸酶）组成的人工设计途径。更重要的是，我们通过对多种策略的系统评估，设计了细胞工厂来提高 5-MU 产量，并且作为概念证明，我们进一步开发了无抗生素发酵策略来实现 5-MU 产量（10.71 g/L） ）在MB229（一种菌株）中。值得注意的是，我们还建立了一个多功能且强大的平台，利用工程技术来高效生产多样化的 UMP 衍生化学品。这项研究为未来工程作为合成生物学平台铺平了道路，以加速获取 UMP 衍生的化学多样性。