Genetic circuits for feedback control of gamma-aminobutyric acid biosynthesis in probiotic Escherichia coli Nissle 1917.
Genetic circuits for feedback control of gamma-aminobutyric acid biosynthesis in probiotic Escherichia coli Nissle 1917.
复制标题
用于反馈控制益生菌大肠杆菌 Nissle 中 γ-氨基丁酸生物合成的遗传电路 1917。
DOI：
10.1101/2023.06.09.544351
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Andrews,LaurenB
中科院分区：
文献类型：
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作者：
Lebovich,Matthew;Andrews,LaurenB
工程微生物，如益生菌菌株Escherichia coliNissle 1917(ECN)，提供了一种感知和调节胃肠道代谢物或治疗药物浓度的策略。在这里，我们提出了一种方法，通过实施负反馈的遗传电路来调节ECN中与抑郁相关的代谢物伽马氨基丁酸(GABA)的产生。我们通过过量表达谷氨酸脱羧酶来改造ECN来生产GABA，并应用细胞内GABA生物传感器来确定促进GABA生物合成的生长条件。接下来，我们使用特征化的遗传编码NOT门来构建具有分层反馈的遗传电路，以控制GABA生物合成的速度和产生的GABA浓度。展望未来，这一方法可能被用于设计微生物代谢物生物合成的反馈控制，以获得可设计的智能微生物作为生命疗法。
Engineered microorganisms such as the probiotic strainEscherichia coliNissle 1917 (EcN) offer a strategy to sense and modulate the concentration of metabolites or therapeutics in the gastrointestinal tract. Here, we present an approach to regulate the production of the depression-associated metabolite gamma-aminobutyric acid (GABA) in EcN using genetic circuits that implement negative feedback. We engineered EcN to produce GABA by overexpressing glutamate decarboxylase and applied an intracellular GABA biosensor to identify growth conditions that improve GABA biosynthesis. We next employed characterized genetically encoded NOT gates to construct genetic circuits with layered feedback to control the rate of GABA biosynthesis and the concentration of GABA produced. Looking ahead, this approach may be utilized to design feedback control of microbial metabolite biosynthesis to achieve designable smart microbes that act as living therapeutics.