Dynamic control of toxic natural product biosynthesis by an artificial regulatory circuit
Dynamic control of toxic natural product biosynthesis by an artificial regulatory circuit
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DOI：
10.1016/j.ymben.2019.12.002
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发表时间：
2020-01-01
影响因子：
8.4
通讯作者：
Tang, Shuang-Yan
中科院分区：
文献类型：
--
作者：
Liang, Chaoning;Zhang, Xuanxuan;Tang, Shuang-Yan
为了模仿自然界中微妙调节的代谢以提高效率，在实验室工程中动态控制多层代谢网络的人工和定制调节组件至关重要。为此，通过定向进化开发了一种用于控制香草醛生物合成途径的新型调控元件，该元件对产物香草醛和底物阿魏酸均具有不同的响应能力。这种调节成分通过动态控制细胞内底物和产物浓度来促进途径表达。由于香草醛是一种抗菌化合物，低途径表达和香草醛形成水平使得早期细胞生长更好，而后期产物反馈激活途径表达显着提高了生物合成效率。这种新颖的多层动态控制被证明可以有效管理细胞生长和生产之间的权衡，与传统或群体感应启动子控制的途径相比，可以改善细胞生长和香草醛生产。除了迄今为止报道的基于生物合成中间体传感和群体传感的动态控制之外，由设计的响应多个信号的调节组件实现的多层动态控制显示出广泛应用的潜力。
To mimic the delicately regulated metabolism in nature for improved efficiency, artificial and customized regulatory components for dynamically controlling metabolic networks in multiple layers are essential in laboratory engineering. For this purpose, a novel regulatory component for controlling vanillin biosynthetic pathway was developed through directed evolution, which was responsive to both the product vanillin and substrate ferulic acid, with different capacities. This regulatory component facilitated pathway expression via dynamic control of the intracellular substrate and product concentrations. As vanillin is an antimicrobial compound, low pathway expression and vanillin formation levels enabled better cell growth at an early stage, and the product feedback-activated pathway expression at later stages significantly improved biosynthesis efficiency. This novel multiple-layer dynamic control was demonstrated effective in managing the trade-off between cell growth and production, leading to improved cell growth and vanillin production compared to the conventional or quorum-sensing promoter-controlled pathway. The multiple-layer dynamic control enabled by designed regulatory components responsive to multiple signals shows potential for wide applications in addition to the dynamic controls based on biosynthetic intermediate sensing and quorum sensing reported to date.