焊剂(冶金)
异源的
代谢工程
生物反应器
生物化学
大肠杆菌
生物
细菌
糖酵解
产量(工程)
化学
代谢途径
新陈代谢
基因
遗传学
材料科学
有机化学
冶金
植物
作者
Apoorv Gupta,Irene Reizman,Christopher R. Reisch,Kristala L. J. Prather
摘要
An inducer-free quorum-sensing circuit is applied to control endogenous bacterial gene expression and improve yields of a range of products. Metabolic engineering of microorganisms to produce desirable products on an industrial scale can result in unbalanced cellular metabolic networks that reduce productivity and yield. Metabolic fluxes can be rebalanced using dynamic pathway regulation, but few broadly applicable tools are available to achieve this. We present a pathway-independent genetic control module that can be used to dynamically regulate the expression of target genes. We apply our module to identify the optimal point to redirect glycolytic flux into heterologous engineered pathways in Escherichia coli, resulting in titers of myo-inositol increased 5.5-fold and titers of glucaric acid increased from unmeasurable to >0.8 g/L, compared to the parent strains lacking dynamic flux control. Scaled-up production of these strains in benchtop bioreactors resulted in almost ten- and fivefold increases in specific titers of myo-inositol and glucaric acid, respectively. We also used our module to control flux into aromatic amino acid biosynthesis to increase titers of shikimate in E. coli from unmeasurable to >100 mg/L.
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