Bioengineering natural product biosynthetic pathways for therapeutic applications.
Bioengineering natural product biosynthetic pathways for therapeutic applications.
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DOI：
10.1016/j.copbio.2012.03.008
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发表时间：
2012-12
影响因子：
7.7
通讯作者：
Ming-Cheng Wu;Brian J. C. Law;B. Wilkinson;Jason Micklefield
中科院分区：
文献类型：
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作者：
Ming-Cheng Wu;Brian J. C. Law;B. Wilkinson;Jason Micklefield
随着下一代DNA测序技术的出现，微生物基因组序列的数量急剧增加，揭示了大量新的生物合成基因簇。基因组学数据为发现新的天然产物提供了巨大的机会，也为指导新的和现有的用于治疗应用的天然产物支架的生物工程。值得注意的是，很明显，绝大多数生物合成基因簇要么沉默，要么产生非常低数量的相应天然产物。因此，必须设计激活非生产性生物合成途径的方法，以提供进一步发展所需的天然产物的数量。此外，基于我们对生物合成装配线酶的不断扩展的机制和结构知识，重新编程生物合成途径的新策略已经出现，从而产生具有潜在改善生物特性的修饰产物的集中文库。在这篇综述中，我们将重点介绍最新的生物工程方法，这些方法已被用于优化产量和增加天然产物支架的结构多样性，以用于未来的临床应用。
With the advent of next-generation DNA sequencing technologies, the number of microbial genome sequences has increased dramatically, revealing a vast array of new biosynthetic gene clusters. Genomics data provide a tremendous opportunity to discover new natural products, and also to guide the bioengineering of new and existing natural product scaffolds for therapeutic applications. Notably, it is apparent that the vast majority of biosynthetic gene clusters are either silent or produce very low quantities of the corresponding natural products. It is imperative therefore to devise methods for activating unproductive biosynthetic pathways to provide the quantities of natural products needed for further development. Moreover, on the basis of our expanding mechanistic and structural knowledge of biosynthetic assembly-line enzymes, new strategies for re-programming biosynthetic pathways have emerged, resulting in focused libraries of modified products with potentially improved biological properties. In this review we will focus on the latest bioengineering approaches that have been utilised to optimise yields and increase the structural diversity of natural product scaffolds for future clinical applications.