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合成生物学方法在天然产物生物合成中的应用。

Synthetic biological approaches to natural product biosynthesis.

机构信息

Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, CA 90095, United States.

出版信息

Curr Opin Biotechnol. 2012 Oct;23(5):736-43. doi: 10.1016/j.copbio.2011.12.016. Epub 2012 Jan 3.

Abstract

Small molecules produced in Nature possess exquisite chemical diversity and continue to be an inspiration for the development of new therapeutic agents. In their host organisms, natural products are assembled and modified using dedicated biosynthetic pathways. By rationally reprogramming and manipulating these pathways, unnatural metabolites containing enhanced structural features that were otherwise inaccessible can be obtained. Additionally, new chemical entities can be synthesized by developing the enzymes that carry out these complicated chemical reactions into biocatalysts. In this review, we will discuss a variety of combinatorial biosynthetic strategies, their technical challenges, and highlight some recent (since 2007) examples of rationally designed metabolites, as well as platforms that have been established for the production and modification of clinically important pharmaceutical compounds.

摘要

自然界中产生的小分子具有精致的化学多样性,并且继续为开发新的治疗药物提供灵感。在其宿主生物中,天然产物使用专用的生物合成途径进行组装和修饰。通过合理地重新编程和操纵这些途径,可以获得具有增强的结构特征的非天然代谢物,这些特征在其他情况下是无法获得的。此外,通过将执行这些复杂化学反应的酶开发成生物催化剂,也可以合成新的化学实体。在这篇综述中,我们将讨论各种组合生物合成策略、它们的技术挑战,并重点介绍一些最近(自 2007 年以来)合理设计的代谢物的例子,以及为生产和修饰临床重要药物化合物而建立的平台。

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