通过在体内连接合成生物学和合成化学来实现 GenoChemetics。,Nature Communications

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通过在体内连接合成生物学和合成化学来实现 GenoChemetics。
Nature Communications ( IF 14.7 ) Pub Date : 2017-08-09 , DOI: 10.1038/s41467-017-00194-3
Sunil V Sharma _{1,

2} , Xiaoxue Tong _{1,

2} , Cristina Pubill-Ulldemolins _{1,

2} , Christopher Cartmell _{1,

2} , Emma J A Bogosyan _{1,

2,

3} , Emma J Rackham _{4,

5} , Enrico Marelli _{1,

2} , Refaat B Hamed _{1,

2} , Rebecca J M Goss _{1,

2}

Affiliation

将合成生物学与合成化学结合为天然产品多样化提供了一种强有力的方法，将两全其美：生物途径的权宜之计和合成能力以及有机合成实现的化学多样性。生物合成途径工程可用于将化学正交标签插入复杂的天然支架中，从而在不采用保护基策略的情况下提供位点选择性修饰的可能性。在这里，我们表明，通过安装足够反应性的手柄（例如，C-Br 键）和开发兼容的温和水化学，可以实现标记代谢物的同步生物合成及其在活培养物中的后续化学修饰。这种方法可能会启用许多新的应用程序：例如，在活细胞中催化卤代代谢物生物合成或在生命系统中产生和跟踪标记代谢物和生物分子的命运的酶的定向进化分析。我们报告了合成生物获得新的自然溴代代谢物以及活培养物中卤代代谢物的双正交交叉偶联。偶联合成生物学和细胞中的化学反应是一项具有挑战性的任务。作者设计了能够产生溴代代谢物的细菌，开发了一种与细胞生长相容的温和 Suzuki-Miyaura 交叉偶联反应，并在活细胞培养物中进行交叉偶联化学。我们报告了合成生物获得新的自然溴代代谢物以及活培养物中卤代代谢物的双正交交叉偶联。偶联合成生物学和细胞中的化学反应是一项具有挑战性的任务。作者设计了能够产生溴代代谢物的细菌，开发了一种与细胞生长相容的温和 Suzuki-Miyaura 交叉偶联反应，并在活细胞培养物中进行交叉偶联化学。我们报告了合成生物获得新的自然溴代代谢物以及活培养物中卤代代谢物的双正交交叉偶联。偶联合成生物学和细胞中的化学反应是一项具有挑战性的任务。作者设计了能够产生溴代代谢物的细菌，开发了一种与细胞生长相容的温和 Suzuki-Miyaura 交叉偶联反应，并在活细胞培养物中进行交叉偶联化学。

"点击查看英文标题和摘要"

Living GenoChemetics by hyphenating synthetic biology and synthetic chemistry in vivo.

Marrying synthetic biology with synthetic chemistry provides a powerful approach toward natural product diversification, combining the best of both worlds: expediency and synthetic capability of biogenic pathways and chemical diversity enabled by organic synthesis. Biosynthetic pathway engineering can be employed to insert a chemically orthogonal tag into a complex natural scaffold affording the possibility of site-selective modification without employing protecting group strategies. Here we show that, by installing a sufficiently reactive handle (e.g., a C-Br bond) and developing compatible mild aqueous chemistries, synchronous biosynthesis of the tagged metabolite and its subsequent chemical modification in living culture can be achieved. This approach can potentially enable many new applications: for example, assay of directed evolution of enzymes catalyzing halo-metabolite biosynthesis in living cells or generating and following the fate of tagged metabolites and biomolecules in living systems. We report synthetic biological access to new-to-nature bromo-metabolites and the concomitant biorthogonal cross-coupling of halo-metabolites in living cultures.Coupling synthetic biology and chemical reactions in cells is a challenging task. The authors engineer bacteria capable of generating bromo-metabolites, develop a mild Suzuki-Miyaura cross-coupling reaction compatible with cell growth and carry out the cross-coupling chemistry in live cell cultures.

更新日期：2017-08-09

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