Towards next-generation cell factories by rational genome-scale engineering

Towards next-generation cell factories by rational genome-scale engineering
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DOI:
10.1038/s41929-022-00836-w
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发表时间:
2022-09
期刊:
影响因子:
37.8
通讯作者:
S. Yilmaz;Á. Nyerges;J. van der Oost;G. Church;Nico J. Claassens
S. Yilmaz;Á. Nyerges;J. van der Oost;G. Church;Nico J. Claassens
中科院分区:
化学1区
文献类型:
--
作者:
S. Yilmaz;Á. Nyerges;J. van der Oost;G. Church;Nico J. Claassens

文献摘要

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代谢工程有望改变化学工业,并支持向循环生物经济的过渡,通过工程细胞生物催化剂,有效地将可持续底物转化为所需的产品。然而,尽管经过数十年的研究,代谢工程的潜力在工业水平上仅在有限的程度上得到实现。为了进一步实现其潜力,必须在系统和全基因组水平上优化细胞工厂的合成和天然代谢网络。在这里,我们讨论的工具和策略,使系统范围内的(半)理性工程。基因组编辑技术的最新进展使越来越多的相关微生物能够进行定向全基因组工程。这种全系统工程可以从机器学习和其他计算机设计方法中受益,并且需要与有效的筛选或选择方法相结合。这些方法有望实现下一代细胞工厂的承诺,以高效,可持续地生产各种产品。
Metabolic engineering holds the promise to transform the chemical industry and to support the transition into a circular bioeconomy, by engineering cellular biocatalysts that efficiently convert sustainable substrates into desired products. However, despite decades of research, the potential of metabolic engineering has only been realized to a limited extent at the industrial level. To further realize its potential, it is essential to optimize the synthetic and native metabolic networks of cell factories at a system and genome-wide level. Here we discuss the tools and strategies enabling system-wide (semi-) rational engineering. Recent advances in genome-editing technologies enable directed genome-wide engineering in a growing number of relevant microorganisms. Such system-wide engineering can benefit from machine learning and other in silico design methods, and it needs to be integrated with efficient screening or selection approaches. These approaches are expected to realize the promise of next-generation cell factories for efficient, sustainable production of a wide range of products.