Chassis optimization as a cornerstone for the application of synthetic biology based strategies in microbial secondary metabolism.
Chassis optimization as a cornerstone for the application of synthetic biology based strategies in microbial secondary metabolism.
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DOI：
10.3389/fmicb.2015.00906
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发表时间：
2015
影响因子：
5.2
通讯作者：
Mendes MV
中科院分区：
文献类型：
--
作者：
Beites T;Mendes MV
细菌基因组测序项目的增加在过去几年中产生了大量的基因组信息库。通过对这些基因组数据的计算机分析，揭示了未知或未表征的代谢物的新型生物合成基因簇，重新引起了人们对细菌生物勘探生物活性化合物的兴趣。然而，这些代谢物中只有一小部分是在实验室控制的条件下产生的;其余的簇代表了等待被“唤醒”的新代谢物的集合。通过异源表达激活表达减少或不表达的生物合成基因簇（称为隐蔽或沉默簇）已成为鉴定和生产新型生物活性分子的策略。以工程原理为核心的合成生物学为开发用于表达生物合成基因簇的有效异源系统提供了极好的框架。然而，其应用中的一个常见问题是主机干扰问题，即，设备和主机之间的不可预测的交互可能会妨碍所需的输出。虽然已经努力开发正交装置，但克服宿主干扰问题的最有效方法是通过基因组简化。在这篇综述中，我们提出了一个概述的策略和工具，用于发展的主机/底盘异源表达的专门代谢物生物合成基因簇。最后，我们介绍了专用主机的概念，作为表达主机发展的下一步。
The increased number of bacterial genome sequencing projects has generated over the last years a large reservoir of genomic information. In silico analysis of this genomic data has renewed the interest in bacterial bioprospecting for bioactive compounds by unveiling novel biosynthetic gene clusters of unknown or uncharacterized metabolites. However, only a small fraction of those metabolites is produced under laboratory-controlled conditions; the remaining clusters represent a pool of novel metabolites that are waiting to be “awaken”. Activation of the biosynthetic gene clusters that present reduced or no expression (known as cryptic or silent clusters) by heterologous expression has emerged as a strategy for the identification and production of novel bioactive molecules. Synthetic biology, with engineering principles at its core, provides an excellent framework for the development of efficient heterologous systems for the expression of biosynthetic gene clusters. However, a common problem in its application is the host-interference problem, i.e., the unpredictable interactions between the device and the host that can hamper the desired output. Although an effort has been made to develop orthogonal devices, the most proficient way to overcome the host-interference problem is through genome simplification. In this review we present an overview on the strategies and tools used in the development of hosts/chassis for the heterologous expression of specialized metabolites biosynthetic gene clusters. Finally, we introduce the concept of specialized host as the next step of development of expression hosts.