Follow the leader: the use of leader peptides to guide natural product biosynthesis.

Follow the leader: the use of leader peptides to guide natural product biosynthesis.
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DOI:
10.1038/nchembio.286
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发表时间:
2010-01
影响因子:
14.8
通讯作者:
van der Donk WA
van der Donk WA
中科院分区:
生物学1区
文献类型:
--
作者:
Oman TJ;van der Donk WA

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在过去的十年里,大量的基因组信息揭示了利用核糖体机制进行天然产物生物合成比最初预期的要广泛得多。几乎所有这些化合物都是通过翻译后修饰一个更大的前体肽,通常包含生物合成酶的行军命令。在这里,我们回顾了现有的信息如何在前体肽序列管理的翻译后剪裁过程中的几个类别的天然产物。此外,我们强调了巨大的潜力,这些领导肽定向生物合成系统提供的工程构象限制和药效团丰富的产品与结构多样性,大大扩大了蛋白质的剧目。
The avalanche of genomic information in the past decade has revealed that natural product biosynthesis using the ribosomal machinery is much more widespread than originally anticipated. Nearly all of these compounds are crafted through posttranslational modifications of a larger precursor peptide that often contains the marching orders for the biosynthetic enzymes. We review here the available information for how the peptide sequences in the precursors govern the posttranslational tailoring processes for several classes of natural products. In addition, we highlight the great potential these leader peptide directed biosynthetic systems offer for engineering conformationally restrained and pharmacophore-rich products with structural diversity that greatly expands the proteinogenic repertoire.
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