异源的
合成生物学
前馈
代谢途径
碳通量
系统生物学
计算机科学
生物
计算生物学
酶
生物化学
控制工程
工程类
基因
生态学
生态系统
作者
Tian Jiang,Chenyi Li,Yusong Zou,Jianli Zhang,Qi Gan,Yajun Yan
标识
DOI:10.1016/j.ymben.2022.08.009
摘要
Endogenous metabolic pathways in microbial cells are usually precisely controlled by sophisticated regulation networks. However, the lack of such regulations when introducing heterologous pathways in microbial hosts often causes unbalanced enzyme expression and carbon flux distribution, hindering the construction of highly efficient microbial biosynthesis systems. Here, using naringenin as the target compound, we developed an Autonomous Cascaded Artificial Dynamic (AutoCAD) regulation system to automatically coordinate the pathway expression and redirect carbon fluxes for enhanced naringenin production. The AutoCAD regulation system, consisting of both intermediate-based feedforward and product-based feedback control genetic circuits, resulted in a 16.5-fold increase in naringenin titer compared with the static control. Fed-batch fermentation using the strain with AutoCAD regulation further enhanced the naringenin titer to 277.2 mg/L. The AutoCAD regulation system, with intermediate-based feedforward control and product-triggered feedback control, provides a new paradigm of developing complicated cascade dynamic control to engineer heterologous pathways.
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