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Regulation underlying hierarchical and simultaneous utilization of carbon substrates by flux sensors in Escherichia coli.
Nature Microbiology ( IF 20.5 ) Pub Date : 2019-12-09 , DOI: 10.1038/s41564-019-0610-7
Hiroyuki Okano 1 , Rutger Hermsen 2 , Karl Kochanowski 3, 4, 5 , Terence Hwa 1
Affiliation  

Many microorganisms exhibit nutrient preferences, exemplified by the 'hierarchical' consumption of certain carbon substrates. Here, we systematically investigate under which physiological conditions hierarchical substrate utilization occurs and its mechanisms of implementation. We show utilization hierarchy of Escherichia coli to be ordered by the carbon-uptake flux rather than the identity of the substrates. A detailed study of glycerol uptake finds that it is fully suppressed if the uptake flux of another glycolytic substrate exceeds a threshold, which is set to the influx obtained when grown on glycerol alone. Below this threshold, limited glycerol uptake is 'supplemented' such that the total carbon uptake is maintained at the threshold. This behaviour results from total-flux feedback mediated by cAMP-Crp signalling but also requires inhibition by the regulator fructose 1,6-bisphosphate, which senses the upper-glycolytic flux and ensures that glycerol uptake defers to other glycolytic substrates but not to gluconeogenic ones. A quantitative model reproduces all of the observed utilization patterns, including those of key mutants. The proposed mechanism relies on the differential regulation of uptake enzymes and requires a specific operon organization. This organization is found to be conserved across related species for several uptake systems, suggesting the deployment of similar mechanisms for hierarchical substrate utilization by a spectrum of microorganisms.

中文翻译:

大肠杆菌中通量传感器对碳底物分级和同时利用的调控。

许多微生物表现出对营养的偏好,例如某些碳底物的“分级”消耗。在这里,我们系统地研究了在哪些生理条件下发生分层底物利用及其实施机制。我们显示了大肠杆菌的利用层次结构是由碳吸收通量而不是底物的特性来排序的。对甘油摄取的详细研究发现,如果另一种糖酵解底物的摄取通量超过阈值,则它会被完全抑制,阈值设置为单独在甘油上生长时获得的流入量。低于这个阈值,有限的甘油吸收被“补充”,使得总碳吸收保持在阈值。这种行为是由 cAMP-Crp 信号介导的总通量反馈引起的,但也需要调节果糖 1,6-二磷酸的抑制,它感知上糖酵解通量并确保甘油摄取服从其他糖酵解底物而不是糖异生底物. 定量模型再现了所有观察到的利用模式,包括关键突变体的利用模式。所提出的机制依赖于摄取酶的差异调节,并且需要特定的操纵子组织。发现这种组织在几个吸收系统的相关物种中是保守的,这表明部署了类似的机制用于一系列微生物的分级底物利用。它感知上糖酵解通量并确保甘油摄取服从其他糖酵解底物而不是糖异生底物。定量模型再现了所有观察到的利用模式,包括关键突变体的利用模式。所提出的机制依赖于摄取酶的差异调节,并且需要特定的操纵子组织。发现这种组织在几个吸收系统的相关物种中是保守的,这表明部署了类似的机制用于一系列微生物的分级底物利用。它感知上糖酵解通量并确保甘油摄取服从其他糖酵解底物而不是糖异生底物。定量模型再现了所有观察到的利用模式,包括关键突变体的利用模式。所提出的机制依赖于摄取酶的差异调节,并且需要特定的操纵子组织。发现这种组织在几个吸收系统的相关物种中是保守的,这表明部署了类似的机制用于一系列微生物的分级底物利用。所提出的机制依赖于摄取酶的差异调节,并且需要特定的操纵子组织。发现这种组织在几个吸收系统的相关物种中是保守的,这表明部署了类似的机制用于一系列微生物的分级底物利用。所提出的机制依赖于摄取酶的差异调节,并且需要特定的操纵子组织。发现这种组织在几个吸收系统的相关物种中是保守的,这表明部署了类似的机制用于一系列微生物的分级底物利用。
更新日期:2019-12-11
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