Reinvigorating natural product combinatorial biosynthesis with synthetic biology.
Reinvigorating natural product combinatorial biosynthesis with synthetic biology.
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DOI：
10.1038/nchembio.1893
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发表时间：
2015-09
影响因子：
14.8
通讯作者：
Yoon YJ
中科院分区：
文献类型：
--
作者：
Kim E;Moore BS;Yoon YJ
天然产品在药物发现工作和了解人类健康方面继续发挥着关键作用。通过组合生物合成（通过操纵生物合成酶改变官能团，区域化学和支架骨架）扩展自然化学的能力为创造天然产物类似物提供了独特的机会。结合新兴的合成生物学技术有可能进一步加速组合生物合成的完善，成为天然化学药物线索多元化的强大平台。二十年后，该领域的起源，我们讨论了目前的局限性，现实和组合生物合成的最新技术，包括生物合成酶的底物特异性工程和生物合成途径的异源表达系统的发展。我们还提出了一个新的观点，天然产物的组合生物合成，可以重振药物发现，通过使用合成生物学与合成化学相结合。
Natural products continue to play a pivotal role in drug discovery efforts and in understanding human health. The ability to extend nature’s chemistry through combinatorial biosynthesis – altering functional groups, regiochemistry, and scaffold backbones through manipulation of biosynthetic enzymes – offers unique opportunities to create natural product analogues. Incorporating emerging synthetic biology techniques has the potential to further accelerate the refinement of combinatorial biosynthesis as a robust platform for the diversification of natural chemical drug leads. Two decades after the field originated, we discuss the current limitations, realities, and the state of the art of combinatorial biosynthesis, including the engineering of substrate specificity of biosynthetic enzymes and the development heterologous expression systems for biosynthetic pathways. We also propose a new perspective for the combinatorial biosynthesis of natural products that could reinvigorate drug discovery by using synthetic biology in combination with synthetic chemistry.