Natural Products - Natural Products: Discourse, Diversity, and Design
Natural Products - Natural Products: Discourse, Diversity, and Design
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天然产品 - 天然产品：话语、多样性和设计
DOI：
10.1002/9781118794623.ch19
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Breitling R
中科院分区：
文献类型：
--
作者：
Breitling R
其生物合成途径的多样性和天然模块化使天然产物成为合成生物学方法的有吸引力但具有挑战性的目标。在这里，我们讨论了该领域的现状，强调了最近的进展和剩余的瓶颈。对大部分微生物多样性的天然产物生物合成能力的全球基因组评估提供了对可用的天然部分库的第一次调查，并确定了进一步工程的进化设计规则。用于化合物和途径检测和表征的方法越来越多地基于合成生物学工具开发，有助于将基因组信息加速翻译成用于途径组装的可用构件。在我们对潜在的生物化学和酶机制的理解的快速进展的指导下，通过合理地多样化天然产物，各种各样的方法也可用于进入化学空间的更大部分。增强的基因组组装和编辑工具，适应天然产物研究的需要，促进实现雄心勃勃的工程策略，从组合文库生成到产品滴度的高通量优化。总之，这些工具和概念有助于新一代振兴天然产品研究的出现。
The diversity and natural modularity of their biosynthetic pathways has turned natural products into attractive, but challenging, targets for synthetic biology approaches. Here, we discuss the current state of the field, highlighting recent advances and remaining bottlenecks. Global genomic assessments of natural product biosynthetic capacities across large parts of microbial diversity provide a first survey of the available natural parts libraries and identify evolutionary design rules for further engineering. Methods for compound and pathway detection and characterization are developed increasingly on the basis of synthetic biology tools, contributing to an accelerated translation of genomic information into usable building blocks for pathway assembly. A wide range of methods is also becoming available for accessing ever larger parts of chemical space by rational diversification of natural products, guided by rapid progress in our understanding of the underlying biochemistry and enzymatic mechanisms. Enhanced genome assembly and editing tools, adapted to the needs of natural products research, facilitate the realization of ambitious engineering strategies, ranging from combinatorial library generation to high-throughput optimization of product titers. Together, these tools and concepts contribute to the emergence of a new generation of revitalized natural product research.