Cell-Free Exploration of the Natural Product Chemical Space.

Cell-Free Exploration of the Natural Product Chemical Space.
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DOI:
10.1002/cbic.202000452
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发表时间:
2021-01-05
期刊:
Chembiochem : a European journal of chemical biology
影响因子:
--
通讯作者:
Jewett MC
Jewett MC
中科院分区:
其他
文献类型:
--
作者:
Bogart JW;Cabezas MD;Vögeli B;Wong DA;Karim AS;Jewett MC

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天然产物和次生代谢物构成了生物有机体不可缺少的资源,它们已经改变了医学、农业和生物技术领域。然而,高通量DNA测序和计算分析的最新进展表明,绝大多数天然产物仍未被发现。为了加速天然产物的发现,用于开发强大催化网络的无细胞代谢工程方法正被重新用于获取新的化学支架和能够执行多种化学反应的新酶。这些酶可以作为灵活的生物催化工具,进一步扩大天然产物和次生代谢物的独特化学空间,并为未来制造这些分子提供更可持续的途径。在这里,我们重点介绍了无细胞系统中天然产物生物合成的例子,并提出了无细胞技术如何促进我们访问和修改这些结构以改变合成和化学生物学的能力。
Natural products and secondary metabolites comprise an indispensable resource from living organisms that have transformed areas of medicine, agriculture, and biotechnology. Recent advances in high-throughput DNA sequencing and computational analysis, however, suggests that a vast majority of natural products remain undiscovered. To accelerate the natural product discovery pipeline, cell-free metabolic engineering approaches used to develop robust catalytic networks are being repurposed to access new chemical scaffolds, and new enzymes capable of performing diverse chemistries. Such enzymes may serve as flexible biocatalytic tools to further expand the unique chemical space of natural products and secondary metabolites and provide a more sustainable route to manufacture these molecules in the future. Here, we highlight select examples of natural product biosynthesis in cell-free systems and propose how cell-free technologies could facilitate our ability to access and modify these structures to transform synthetic and chemical biology.
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