历久弥新：进化中的代谢工程

An evolving and flourishing metabolic engineering

摘要:

20世纪90年代，Bailey及Stephanopoulos等提出了经典代谢工程的理念，旨在利用DNA重组技术对代谢网络进行改造，以达到细胞性能改善，目标产物增加的目的。自代谢工程诞生以来的30年，生命科学蓬勃发展，基因组学、系统生物学、合成生物学等新学科不断涌现，为代谢工程的发展注入了新的内涵与活力。经典代谢工程研究已进入到前所未有的系统代谢工程阶段。组学技术、基因组代谢模型、元件组装、回路设计、动态控制、基因组编辑等合成生物学工具与策略的应用，大大提升了复杂代谢的设计与合成能力；机器学习的介入以及进化工程与代谢工程的结合，为系统代谢工程的未来开辟了新的方向。文中对过去30年代谢工程的发展趋势作了梳理，介绍了代谢工程在发展中不断创新的理论与方法及其应用。

Abstract:

In 1990s, Bailey and Stephanopoulos put forward the concept of classic metabolic engineering, aiming to use DNA recombination technology to rewire metabolic network to achieve improved cell performance and increased target products. In the last 30 years since the birth of metabolic engineering, life science have flourished, and new disciplines such as genomics, systems biology and synthetic biology have emerged, injecting new connotations and vitality into the development of metabolic engineering. Classic metabolic engineering research has entered into an unprecedented stage of systems metabolic engineering. The application of synthetic biology tools and strategies, such as omics technology, genomic-scale metabolic model, parts assembly, circuits design, dynamic control, genome editing and many others, have greatly improved the design, build, and rewiring capabilities of complex metabolism. The intervention of machine learning and the combination of evolutionary engineering and metabolic engineering will further promote the development of systems metabolic engineering. This paper analyzes the development of metabolic engineering in the past 30 years and summarizes the novel theories, techniques, strategies, and applications of metabolic engineering that have emerged over the past 30 years.