Glucose becomes one of the worst carbon sources for E.coli on poor nitrogen sources due to suboptimal levels of cAMP.
Glucose becomes one of the worst carbon sources for E.coli on poor nitrogen sources due to suboptimal levels of cAMP.
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DOI：
10.1038/srep24834
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发表时间：
2016-04-25
影响因子：
4.6
通讯作者：
Alon U
中科院分区：
文献类型：
--
作者：
Bren A;Park JO;Towbin BD;Dekel E;Rabinowitz JD;Alon U
在大多数情况下，葡萄糖是大肠杆菌的最佳碳源：它比其他糖类生长得更快，并且首先在糖混合物中被消耗。在这里，我们确定了大肠杆菌菌株在葡萄糖上比在其他糖上生长得慢的条件，即当单一氨基酸（精氨酸、谷氨酸或脯氨酸）是唯一氮源时。在含有这些氮源的糖混合物中，大肠杆菌仍然首先消耗葡萄糖，但在耗尽葡萄糖后生长得更快而不是更慢，从而产生反向双轴转变。我们将这种违反直觉的行为归因于代谢失衡：包括 α-酮戊二酸在内的 TCA 循环代谢物水平较高，而关键调节分子 cAMP 的水平较低。通过实验增加 cAMP 水平（通过添加外部 cAMP、通过遗传扰乱 cAMP 回路或通过抑制葡萄糖摄取）来增加生长速率。因此，cAMP 控制电路似乎存在一个“缺陷”，导致在环境罕见的条件下生长缓慢。
In most conditions, glucose is the best carbon source for E. coli: it provides faster growth than other sugars, and is consumed first in sugar mixtures. Here we identify conditions in which E. coli strains grow slower on glucose than on other sugars, namely when a single amino acid (arginine, glutamate, or proline) is the sole nitrogen source. In sugar mixtures with these nitrogen sources, E. coli still consumes glucose first, but grows faster rather than slower after exhausting glucose, generating a reversed diauxic shift. We trace this counterintuitive behavior to a metabolic imbalance: levels of TCA-cycle metabolites including α-ketoglutarate are high, and levels of the key regulatory molecule cAMP are low. Growth rates were increased by experimentally increasing cAMP levels, either by adding external cAMP, by genetically perturbing the cAMP circuit or by inhibition of glucose uptake. Thus, the cAMP control circuitry seems to have a ‘bug’ that leads to slow growth under what may be an environmentally rare condition.