Bacterial Cysteine-Inducible Cysteine Resistance Systems
Bacterial Cysteine-Inducible Cysteine Resistance Systems
复制标题
DOI：
10.1128/jb.01039-15
复制
发表时间：
2016-05-01
影响因子：
3.2
通讯作者：
Nonaka, Gen
中科院分区：
文献类型：
--
作者：
Takumi, Kazuhiro;Nonaka, Gen
半胱氨酸向大分子提供硫，并天然存在于许多蛋白质中。由于低浓度的半胱氨酸具有细胞毒性，因此其细胞内浓度受到严格控制。在细菌中，半胱氨酸生物合成通过反馈抑制丝氨酸乙酰转移酶（SAT）和3-磷酸甘油酸脱氢酶（3-PGDH）的活性来调节，并且还通过使用主调节剂CysB诱导半胱氨酸调节子在转录水平上进行调节。在这里，我们描述了两种新的半胱氨酸诱导系统，调节泛菌ananatis，家庭肠杆菌科的成员，显示出巨大的潜力，用于生产生物技术，医疗和工业用途的物质的半胱氨酸抗性。一个基因座，命名为ccdA（以前的PAJ_0331），编码一种新的半胱氨酸诱导型半胱氨酸脱氢酶（CD），降解半胱氨酸，其表达由位于ccdA上游的ccdR（以前的PAJ_0332或ybaO）编码的转录调控因子控制。另一个基因座，命名为cefA（以前的PAJ_3026），编码一种新的半胱氨酸诱导型半胱氨酸外排泵，该泵由位于cefA上游的转录调节因子cefR（以前的PAJ_3027）控制。据我们所知，这是CD和外排泵的表达响应于半胱氨酸而被调节并且直接参与赋予对过量半胱氨酸水平的抗性的第一个实例。我们建议，ccdA和cefA的功能作为安全阀，维持稳态时，内或细胞外半胱氨酸浓度波动。我们的研究结果为优化P. ananatis.IMPORTANCEBecause其毒性，细菌细胞内半胱氨酸水平在生物合成过程中受到严格调节，半胱氨酸和相关生物材料的生产提供了重要的见解。这项工作描述了两种新的半胱氨酸诱导系统，通过降解和外排，半胱氨酸抗性的Pantoea ananatis，家庭肠杆菌科的成员，显示出巨大的潜力，生产用于工业目的的物质，调节的鉴定和表征。我们提出，这种用于感测和调节半胱氨酸水平的新机制是一种安全阀，能够适应细菌内或细胞外半胱氨酸水平的突然变化。我们的研究结果为优化P. ananatis生产半胱氨酸和相关生物材料提供了重要的见解，并深入了解这种植物病原体和相关细菌中的硫/半胱氨酸代谢和调控。
Cysteine donates sulfur to macromolecules and occurs naturally in many proteins. Because low concentrations of cysteine are cytotoxic, its intracellular concentration is stringently controlled. In bacteria, cysteine biosynthesis is regulated by feedback inhibition of the activities of serine acetyltransferase (SAT) and 3-phosphoglycerate dehydrogenase (3-PGDH) and is also regulated at the transcriptional level by inducing the cysteine regulon using the master regulator CysB. Here, we describe two novel cysteine-inducible systems that regulate the cysteine resistance of Pantoea ananatis, a member of the family Enterobacteriaceae that shows great potential for producing substances useful for biotechnological, medical, and industrial purposes. One locus, designated ccdA (formerly PAJ_0331), encodes a novel cysteine-inducible cysteine desulfhydrase (CD) that degrades cysteine, and its expression is controlled by the transcriptional regulator encoded by ccdR (formerly PAJ_0332 or ybaO), located just upstream of ccdA. The other locus, designated cefA (formerly PAJ_3026), encodes a novel cysteine-inducible cysteine efflux pump that is controlled by the transcriptional regulator cefR (formerly PAJ_3027), located just upstream of cefA. To our knowledge, this is the first example where the expression of CD and an efflux pump is regulated in response to cysteine and is directly involved in imparting resistance to excess levels of cysteine. We propose that ccdA and cefA function as safety valves that maintain homeostasis when the intra-or extracellular cysteine concentration fluctuates. Our findings contribute important insights into optimizing the production of cysteine and related biomaterials by P. ananatis.IMPORTANCEBecause of its toxicity, the bacterial intracellular cysteine level is stringently regulated at biosynthesis. This work describes the identification and characterization of two novel cysteine-inducible systems that regulate, through degradation and efflux, the cysteine resistance of Pantoea ananatis, a member of the family Enterobacteriaceae that shows great potential for producing substances useful for industrial purposes. We propose that this novel mechanism for sensing and regulating cysteine levels is a safety valve enabling adaptation to sudden changes in intra-or extracellular cysteine levels in bacteria. Our findings provide important insights into optimizing the production of cysteine and related biomaterials by P. ananatis and also a deep understanding of sulfur/cysteine metabolism and regulation in this plant pathogen and related bacteria.