生物生产
代谢网络
代谢工程
代谢途径
生化工程
计算生物学
细胞代谢
生物
网络拓扑
酶
新陈代谢
异源的
计算机科学
生物化学
基因
工程类
操作系统
作者
Enrico Orsi,Nico J. Claassens,Pablo I. Nikel,Steffen N. Lindner
标识
DOI:10.1016/j.biotechadv.2022.108035
摘要
Metabolism has long been considered as a relatively stiff set of biochemical reactions. This somewhat outdated and dogmatic view has been challenged over the last years, as multiple studies exposed unprecedented plasticity of metabolism by exploring rational and evolutionary modifications within the metabolic network of cell factories. Of particular importance is the emergence of metabolic bypasses, which consist of enzymatic reaction(s) that support unnatural connections between metabolic nodes. Such novel topologies can be generated through the introduction of heterologous enzymes or by upregulating native enzymes (sometimes relying on promiscuous activities thereof). Altogether, the adoption of bypasses resulted in an expansion in the capacity of the host's metabolic network, which can be harnessed for bioproduction. In this review, we discuss modifications to the canonical architecture of central carbon metabolism derived from such bypasses towards six optimization purposes: stoichiometric gain, overcoming kinetic limitations, solving thermodynamic barriers, circumventing toxic intermediates, uncoupling product synthesis from biomass formation, and altering redox cofactor specificity. The metabolic costs associated with bypass-implementation are likewise discussed, including tailoring their design towards improving bioproduction.
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