Engineering membrane and cell-wall programs for tolerance to toxic chemicals: Beyond solo genes.
Engineering membrane and cell-wall programs for tolerance to toxic chemicals: Beyond solo genes.
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DOI：
10.1016/j.mib.2016.06.005
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发表时间：
2016-10
影响因子：
5.4
通讯作者：
Papoutsakis ET
中科院分区：
文献类型：
--
作者：
Sandoval NR;Papoutsakis ET
微生物中的代谢物毒性，特别是在膜上，仍然是生产燃料和化学品的瓶颈。在化学应激下，天然适应机制通过修改膜中的磷脂来对抗超流化。最近在通量组学方面的工作揭示了膜损伤如何负面影响能量代谢的机制，而脂质组学和转录组学分析表明，进化为耐受性的菌株通过多种机制在压力下保持膜流动性，例如掺入环丙烷化脂肪酸、反式不饱和脂肪酸和上调细胞壁生物合成基因。在脂肪酸、肽聚糖和脂多糖的生物合成中进行修饰的工程化菌株已经显示出对外源胁迫的耐受性增加以及具有工业重要性的所需代谢物的产量增加。我们回顾了最近的进展，阐明机制或毒性和耐受性，以及努力工程的细菌膜和细胞壁。
Metabolite toxicity in microbes, particularly at the membrane, remains a bottleneck in the production of fuels and chemicals. Under chemical stress, native adaptation mechanisms combat hyper-fluidization by modifying the phospholipids in the membrane. Recent work in fluxomics reveals the mechanism of how membrane damage negatively affects energy metabolism while lipidomic and transcriptomic analyses show that strains evolved to be tolerant maintain membrane fluidity under stress through a variety of mechanisms such as incorporation of cyclopropanated fatty acids, trans-unsaturated fatty acids, and upregulation of cell wall biosynthesis genes. Engineered strains with modifications made in the biosynthesis of fatty acids, peptidoglycan, and lipopolysaccharide have shown increased tolerance to exogenous stress as well as increased production of desired metabolites of industrial importance. We review recent advances in elucidation of mechanisms or toxicity and tolerance as well as efforts to engineer the bacterial membrane and cell wall.
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