In Salmonella enterica, the sirtuin-dependent protein acylation/deacylation system (SDPADS) maintains energy homeostasis during growth on low concentrations of acetate.
In Salmonella enterica, the sirtuin-dependent protein acylation/deacylation system (SDPADS) maintains energy homeostasis during growth on low concentrations of acetate.
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DOI：
10.1111/j.1365-2958.2011.07566.x
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发表时间：
2011-04
影响因子：
3.6
通讯作者：
Escalante-Semerena JC
中科院分区：
文献类型：
--
作者：
Chan CH;Garrity J;Crosby HA;Escalante-Semerena JC
在大多数细胞中，乙酰辅酶A合成酶(ACS)将醋酸盐激活为乙酰辅酶A(Ac-CoA)。在肠沙门氏菌中，ACS+的表达和活性受到控制。目前尚不清楚为什么依赖sirtuin的蛋白质酰化/去乙酰化系统(SDPADS)控制ACS的活性。在这里，我们表明，在10 mM的醋酸盐上生长，在不能乙酰化(即失活)ACS的肠球菌菌株中诱导ACS+会导致生长停滞，这种情况与乙酰化缺陷菌株中的能量电荷下降(0.17)有关，相对于乙酰化熟练菌株中的能量电荷(0.71)。生长停滞是由ACS活性升高引起的，这一结论得到了一个单一氨基酸变异体(AcsG266S)的分离支持，该变异体的过量生产并没有阻止生长。依赖急性冠脉综合征的ATP消耗，加上AMP水平的上升，阻止了补充ATP池所需的ADP的合成。与这一观点一致的是，形成ADP的Ac-CoA合成系统的过量生产并没有影响PAT缺陷或PAT熟练菌株的生长行为。AcsG266S变种的效率比AcsWT酶低2个数量级，但仍然支持在10 mM的醋酸盐上生长。这项工作提供了第一个证据，表明SDPADS功能有助于细胞在醋酸盐上生长期间保持能量平衡。
Acetyl-coenzyme A synthetase (Acs) activates acetate into acetyl-coenzyme A (Ac-CoA) in most cells. In Salmonella enterica, acs+ expression and Acs activity are controlled. It is unclear why the sirtuin-dependent protein acylation/deacylation system (SDPADS) controls the activity of Acs. Here we show that, during growth on 10 mM acetate, acs+ induction in a S. enterica strain that cannot acetylate (i.e. inactivate) Acs leads to growth arrest, a condition that correlates with a drop in energy charge (0.17) in the acetylation-deficient strain, relative to the energy charge in the acetylation-proficient strain (0.71). Growth arrest was caused by elevated Acs activity, a conclusion supported by the isolation of a single-amino acid variant (AcsG266S), whose overproduction did not arrest growth. Acs-dependent depletion of ATP, coupled with the rise in AMP levels prevented the synthesis of ADP needed to replenish the pool of ATP. Consistent with this idea, overproduction of ADP-forming Ac-CoA synthesizing systems did not affect the growth behavior of Pat-deficient or Pat-proficient strains. The AcsG266S variant was >2 orders of magnitude less efficient than the AcsWT enzyme, but still supported growth on 10 mM acetate. This work provides the first evidence that SDPADS function helps cells maintain energy homeostasis during growth on acetate.
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影响因子：
3.2
作者：
BERKOWIT.D;HUSHON, JM;AMES, BN
通讯作者：
AMES, BN
影响因子：
2.9
作者：
Horswill, AR;Escalante-Semerena, JC
通讯作者：
Escalante-Semerena, JC
影响因子：
3.2
作者：
Gardner, Jeffrey G.;Escalante-Semerena, Jorge C.
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影响因子：
2.9
作者：
FREY, PA;ARABSHAHI, A
通讯作者：
ARABSHAHI, A
影响因子：
3.6
作者：
Crosby HA;Heiniger EK;Harwood CS;Escalante-Semerena JC
通讯作者：
Escalante-Semerena JC