The future of metabolic engineering and synthetic biology: towards a systematic practice.
The future of metabolic engineering and synthetic biology: towards a systematic practice.
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DOI：
10.1016/j.ymben.2012.02.001
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发表时间：
2012-05
影响因子：
8.4
通讯作者：
Stephanopoulos, Gregory
中科院分区：
文献类型：
--
作者：
Yadav, Vikramaditya G.;De Mey, Marjan;Lim, Chin Giaw;Ajikumar, Parayil Kumaran;Stephanopoulos, Gregory
关键词：
工业生物技术有望在未来几年内彻底改变传统的化学制造业，这主要是由于我们在重新设计细胞代谢方面取得了卓越的进展。然而，大多数代谢工程的成功都局限于在E. coli和革兰氏阳性菌S.啤酒。这一发展的主要原因是代谢工程，特别是次级代谢工程，已经下降到一个示范的集合，而不是一个系统的实践与可推广的工具。合成生物学，一个较新的发展，面临着类似的批评。在此，我们试图建立一个框架，围绕这个框架，生物反应工程可以像化学反应工程一样系统化。这项工作的核心是一种新的二级代谢工程方法，称为“多变量模块化代谢工程”（MMME），其新奇在于通过将代谢网络重新定义为不同模块的集合来评估和消除调节和途径瓶颈。在介绍了MMME的核心原理后，我们将介绍一些可能成为其促进剂的次级代谢工程的最新进展。随着基因从头合成成本的不断降低，生物信息学工具在生物数据挖掘、分类和分析方面的应用不断提高，以及研究工具的日益灵敏和完善，微生物代谢工程的成熟将成为一个自动催化的过程。在这些进展的鼓舞下，世界各地的研究小组将以新的活力迎接在简单宿主中生产次级代谢物的挑战，从而增加使用代谢工程合成的产品的范围。
Industrial biotechnology promises to revolutionize conventional chemical manufacturing in the years ahead, largely owing to the excellent progress in our ability to re-engineer cellular metabolism. However, most successes of metabolic engineering have been confined to over-producing natively synthesized metabolites in E. coli and S. cerevisiae. A major reason for this development has been the descent of metabolic engineering, particularly secondary metabolic engineering, to a collection of demonstrations rather than a systematic practice with generalizable tools. Synthetic biology, a more recent development, faces similar criticisms. Herein, we attempt to lay down a framework around which bioreaction engineering can systematize itself just like chemical reaction engineering. Central to this undertaking is a new approach to engineering secondary metabolism known as ‘multivariate modular metabolic engineering’ (MMME), whose novelty lies in its assessment and elimination of regulatory and pathway bottlenecks by re-defining the metabolic network as a collection of distinct modules. After introducing the core principles of MMME, we shall then present a number of recent developments in secondary metabolic engineering that could potentially serve as its facilitators. It is hoped that the ever-declining costs of de novo gene synthesis; the improved use of bioinformatic tools to mine, sort and analyze biological data; and the increasing sensitivity and sophistication of investigational tools will make the maturation of microbial metabolic engineering an autocatalytic process. Encouraged by these advances, research groups across the world would take up the challenge of secondary metabolite production in simple hosts with renewed vigor, thereby adding to the range of products synthesized using metabolic engineering.
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DOI：
10.1126/science.1191652
发表时间：
2010-10-01
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Ajikumar PK;Xiao WH;Tyo KE;Wang Y;Simeon F;Leonard E;Mucha O;Phon TH;Pfeifer B;Stephanopoulos G
通讯作者：
Stephanopoulos G
影响因子：
3.8
作者：
Lee, Ju Young;Yang, Kyung Seok;Kim, Sun Chang
通讯作者：
Kim, Sun Chang
影响因子：
8.4
作者：
Jones, Kristala L.;Kim, Seon-Won;Keasling, J. D.
通讯作者：
Keasling, J. D.
影响因子：
3.5
作者：
De Mey M;Maertens J;Lequeux GJ;Soetaert WK;Vandamme EJ
通讯作者：
Vandamme EJ
影响因子：
8.4
作者：
Anthony, Jennifer R.;Anthony, Larry C.;Keasling, Jay D.
通讯作者：
Keasling, Jay D.