Dynamic metabolic engineering: New strategies for developing responsive cell factories.
Dynamic metabolic engineering: New strategies for developing responsive cell factories.
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DOI：
10.1002/biot.201400422
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发表时间：
2015-09
影响因子：
4.7
通讯作者：
Prather KL
中科院分区：
文献类型：
--
作者：
Brockman IM;Prather KL
代谢工程策略能够提高微生物中自然产生的各种有价值的小分子的产量和滴度，以及通过异源途径产生的小分子。通常，这些方法集中在基因的上调和下调上，以重新分配稳态途径通量，但最近一些研究小组已经开发出动态调节策略，允许根据细胞或发酵培养基中不断变化的条件重新平衡通量。本文综述了最近发表的一些与动态代谢工程策略相关的工作，并探讨了高通量筛选和合成生物学的进展如何支持新的动态系统的开发。动态基因表达谱可以更好地管理生长和生产之间的权衡，并有助于避免不需要的中间产物的积累。与静态控制相比，这种方法的实施更为复杂，但筛选技术和DNA合成的进步将继续推动这一领域的创新。
Metabolic engineering strategies have enabled improvements in yield and titer for a variety of valuable small molecules produced naturally in microorganisms, as well as those produced via heterologous pathways. Typically, the approaches have been focused on up- and downregulation of genes to redistribute steady-state pathway fluxes, but more recently a number of groups have developed strategies for dynamic regulation, which allows rebalancing of fluxes according to changing conditions in the cell or the fermentation medium. This review highlights some of the recently published work related to dynamic metabolic engineering strategies and explores how advances in high-throughput screening and synthetic biology can support development of new dynamic systems. Dynamic gene expression profiles allow trade-offs between growth and production to be better managed and can help avoid build-up of undesired intermediates. The implementation is more complex relative to static control, but advances in screening techniques and DNA synthesis will continue to drive innovation in this field.