2024, Vol. 64中国科学院微生物研究所，中国微生物学会
文章信息
- 张博, 潘佳园, 柳志强, 郑裕国. 2024
- ZHANG Bo, PAN Jiayuan, LIU Zhiqiang, ZHENG Yuguo.
- 蛋白质过硫化修饰研究进展
- Research progress in protein persulfidation
- 微生物学报, 64(5): 1348-1363
- Acta Microbiologica Sinica, 64(5): 1348-1363
-
文章历史
- 收稿日期：2023-10-16
- 网络出版日期：2024-02-26
引用本文 |
2. 浙江工业大学生物工程学院 浙江省生物有机合成技术研究重点实验室, 浙江 杭州 310014
2. Key Laboratory of Bioorganic Synthesis of Zhejiang Province, College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310014, Zhejiang, China
随着对生物体内硫代谢越来越多的深入研究，多种与含硫化合物相关的代谢调控与功能机制已被发现。过硫化修饰是近年来发现的一种重要蛋白质翻译后修饰，具有参与维持细胞正常生理活动和调节代谢稳态的作用。硫化氢(hydrogen sulfide, H2S)和活性硫(reactive sulfur species, RSS)被认为能够直接参与细胞的信号调控，两者在功能发挥上具有紧密联系。在生物体内，RSS与H2S具有多种生成转化途径，包括三巯基丙酮酸转移酶(3-mercaptopyruvate sulfurtransferase, 3-MST)、胱硫醚β-合成酶(cystathionine β-synthase, CBS)、胱硫醚γ-裂解酶(cystathionine γ-lyase, CSE)、半胱氨酸脱硫酶(L-cysteine desulfhydrases, CDs)介导的H2S生成途径，以及硫氧化系统、醌氧还原酶等介导的RSS生成途径，其在不同的细胞间也存在一定的差异。通过调节细胞内H2S/RSS平衡，过硫化修饰在微生物硫稳态调控中发挥重要作用。
1 过硫化修饰简介蛋白质翻译后修饰(protein translational modifications, PTMs)是指在蛋白质合成过程中或合成后酶介导的功能基团共价添加来增加蛋白质组的功能多样性[1]。目前磷酸化、乙酰化、甲基化等PTMs已被广泛报道，近年来，一种新的PTMs——过硫化修饰被发现能够广泛影响蛋白质的功能。过硫化修饰是一种可逆的氧化还原依赖性蛋白质修饰，通常蛋白质的半胱氨酸残基作为氧化还原最敏感的氨基酸残基，其活性受到pKa的影响，其氧化还原状态通常会改变蛋白质的结构和功能[2]。理论上，H2S中的硫原子与蛋白质半胱氨酸残基的−SH基团处于相同的还原状态，因此H2S不能直接与蛋白质半胱氨酸残基的−SH基团反应生成过硫化物[3]，然而H2S可以与蛋白质中半胱氨酸残基的一些氧化形式，如磺酸、亚硝基硫醇反应生成过硫化物[4-5]。
过硫化修饰是一种重要的PTMs，具有参与维持细胞正常生理活动和代谢调控稳态的作用，在保护蛋白质的正常功能、信号的传递以及维持细胞正常的生理代谢中扮演着重要的角色，蛋白质过硫化修饰机制如图 1所示[6]：(1) 蛋白质的半胱氨酸残基不能直接与H2S发生过硫化修饰反应[5]；(2) 在生理条件下，低pKa蛋白质半胱氨酸残基位点通常以硫酸盐阴离子(SO42−)的形式存在，对氧化还原高度敏感[7-8]，它们的氧化形式，例如磺酸(−SOH)和亚硝基硫醇(−SNO)，易与H2S反应生成过硫化物(−SSH)[9]；(3) H2S可以与半胱氨酸二硫化物(−S−S−)反应形成过硫化物(−SSH)；(4) −SH能够与有机过硫化物(RSSH)反应生成−SSH；(5) 经过过硫化修饰的半胱氨酸残基可以通过硫氧还蛋白(thioredoxin, Trx)进行蛋白质脱硫反应[10]。越来越多的证据表明，蛋白质的过硫化修饰能够使关键半胱氨酸残基在氧化应激下抵抗不可逆氧化[11]。近期研究发现，在化学品生物合成过程中，由代谢改造引起的细胞生理应激反应，如代谢通量压力、中间代谢物或产物胁迫、氧胁迫等，以及活性氧(reactive oxygen species, ROS)的产生可能均与过硫化修饰相关[12-13]。这一点在L-半胱氨酸的代谢改造中更为明显，多个研究已经证实了，含硫氨基酸代谢、过硫化修饰、细胞胁迫间紧密关联[14-16]。
|
| 图 1 蛋白质过硫化修饰机理示意图[6] Figure 1 Schematic representation of the mechanism underlying protein persulfidation[6]. (1) Protein thiols cannot react with H2S directly; (2) H2S can react with sulfenic acids and S-nitrosated for sulfhydration; (3) H2S reacts with cysteine disulfides (−S−S) for sulfhydration formation; (4) −SH reacts with RSSH to generate −SSH; (5) Protein persulfidation could potentially be reduced by thioredoxin/thioredoxin reductase system (Trx/TrxR). |
2 H2S及RSS
H2S一直以来被认为是对环境及生命有毒的物质，直至20世纪末，H2S作为一种神经调节剂的信号传导功能才首次被确认[17]。H2S具有二元性，其浓度超过一定阈值是有毒分子，但低于这个阈值，会行使不同的生理功能。H2S在细胞中广泛存在，研究者发现H2S在帮助细菌对抗抗生素[18]、抗氧化、保护细胞对抗凋亡等方面发挥重要作用，因此科学家把H2S看作是继CO、NO之后的第三类信号分子[19]。
H2S的作用机制主要和它的化学性质相关，在生物体内，H2S参与的生化反应主要可以分为3类：(1) 与金属蛋白活性中心的金属离子结合形成配位复合物[20]；(2) 与ROS、活性氮(reactive nitrogen species, RNS)等发生反应[3, 21]；(3) 通过对蛋白质中氧化形式的半胱氨酸残基进行修饰，形成相对应的过硫化物[3] (图 2A)。H2S是小分子物质且极具亲脂性[23]，能够以扩散的方式通过细胞膜，在细胞之间传递信号，由于H2S与蛋白质半胱氨酸残基的−SH基团处于相同还原状态，因此H2S不能直接与蛋白质半胱氨酸残基(−SH)反应生成过硫化物[22]，所以在胞内还有一类特殊的含硫化合物——硫烷硫(reactive sulfane sulfur)，这种形式的硫氧化还原价态通常显示为0价或−1价，也被称为“零价硫”。硫烷硫中反应活性比较强的化合物被称为RSS[24] (图 2B)。RSS包括无机多硫化物(H2Sn, n≥2)、有机多硫化物(RSnR, RSnH, n≥2)以及有机过硫化物(RSSH) (图 2B)，它们在生物体内广泛存在，RSS不能自由通过细胞膜，因此H2S到达靶点后向RSS的转化过程在整个信号传递中发挥了重要的作用[21]。
Kumar等推测H2S和RSS不是对立的个体，H2S在体内可以转化为RSS，二者通常共存，在不同细胞组织间以H2S的形式传递，到达靶点后H2S生成RSS完成对蛋白质的过硫化修饰[26]，因此H2S和RSS是以相互补充的形式共同传递信号[27]。H2S和RSS在维持细胞的生理活动中具有密切的联系，并且越来越多的研究认为RSS是H2S发挥信号分子功能的关键[10, 28-30] (图 3)。Mishanina等也认为H2S是细胞间信号传递的主要形式，而H2S参与的RSS生成是实现信号传递的关键步骤[25]。H2S介导的过硫化修饰已经被认为是调节细胞应激反应从而增强细胞对多种环境应激的耐受性机制之一[31-32]，在维持细胞内稳态以应对各种内外刺激方面发挥着重要作用。
|
| 图 3 H2S与过硫化物(RSSH)作用实现信号传输功能 Figure 3 The interactions between H2S and persulfide (RSSH) for achieving signal transmission function. The H2S diffuses across the cell membrane, where it reacts with oxidized or nitrilized thiol groups to form persulfidation, and is subsequently exported from the cell as HS−. |
2.1 内源H2S的生成
内源H2S的生物合成途径(图 4)包括CBS和CSE途径；3-MST和半胱氨酸氨基转移酶(cysteine aminotransferase, CAT)途径[33-35]，以及大肠杆菌(Escherichia coli)中CDs途径。大多数细菌含有上述一个或者多个H2S生成酶。例如，E. coli含有具有CDs活性的O-乙酰丝氨酸巯基酶A (CysK)、O-乙酰丝氨酸巯基酶B (CysM)、L-半胱氨酸脱巯基酶(TnaA)、3-MST等都会催化L-半胱氨酸分解产生H2S、丙酮酸和氨[36-38]。同时最新研究结果表明[39]，3-MST是蛋白过硫化酶，其半胱氨酸残基可以被过硫化修饰，且其直接参与硫代硫酸盐的转运；铜绿假单胞菌(Pseudomonas aeruginosa)中含有CBS和CSE，敲除铜绿假单胞菌中编码这2种酶的基因后可以大大降低H2S的生成量[40]；而在E. coli中敲除mstA编码的3-MST后，其在LB培养基中产生H2S的能力显著下降[11]，同时E. coli在不同硫源培养基中生成H2S的能力不同，Yang等以硫酸盐和硫代硫酸盐作为不同硫源进行实验时发现，改造后生产L-半胱氨酸的E. coli可利用硫代硫酸盐产生H2S，而以硫酸盐为唯一硫源时未检测到H2S的生成[13]。
|
| 图 4 微生物中H2S生成模型 Figure 4 H2S production model in microorganisms. The processes encompass the transport of thiosulfate and sulfate, the synthesis, metabolism, and degradation of L-cysteine, as well as the degradation of RSS and the transportation of H2S. |
2.1.1 CBS和CSE
细胞中内源H2S的产生主要由L-半胱氨酸和L-同型半胱氨酸的降解产生，而CSE和CBS是其中的2个关键酶[41-42]。CBS在细菌中位于甲硫氨酸循环和转硫途径，使硫参与L-半胱氨酸的合成和分解代谢，进而影响H2S的生物合成，CBS催化L-半胱氨酸与L-同型半胱氨酸生成胱硫醚和H2S，CBS还可以催化2个L-半胱氨酸或2个L-同型半胱氨酸分子之间的交替反应形成H2S[43]。CSE通过催化L-半胱氨酸的β-消除或L-同型半胱氨酸的γ-消除生成H2S[44]。由于在生理条件下L-半胱氨酸的浓度高于L-同型半胱氨酸的浓度，因此L-半胱氨酸的β-消除产生H2S是CSE产生H2S的主要机制[45]。
2.1.2 3-MST和CAT3-MST催化L-半胱氨酸降解是E. coli产生H2S的主要来源，而3-MST的缺失限制了L-半胱氨酸向H2S的转化，使细胞内L-半胱氨酸积累[46]。在线粒体中3-MST和CAT能够协同作用将L-半胱氨酸分解产生H2S，CAT将氨基从L-半胱氨酸转移到α-酮戊二酸中，产生3-巯基丙酮酸(3-mercaptopyruvate, 3-MP)，3-MP是3-MST的底物，3-MST在磷酸吡哆醛(pyridoxal phosphate, PLP)的存在下，接收来自3-MP上的硫原子生成3MST-过硫化物，3MST-过硫化物在含二硫醇的还原剂如Trx或二氢硫辛酸的存在下，将3-MP转化为丙酮酸和H2S[47]。同时通过使用醋酸铅试纸以及基于扭转分子内电荷转移(twisted intramolecular charge transfer, TICT)构建的荧光探针都发现3-MST缺陷细胞产生的H2S量更少[46, 48-49]。
2.1.3 其他途径H2S除了内源合成，还可由RSS还原生成。硫还原菌(sulfur-reducing bacteria, SRB)是一类普遍存在于矿区、水稻和土壤等生态系统中的厌氧菌[50]。SRB的呼吸作用利用无机物(如亚硫酸盐、硫酸盐等)作为电子受体，氢和有机物(如乙酸酯、二氧化碳等)作为电子供体，最终将硫酸盐还原为H2S[51]；而对于多数SRB来说更倾向于利用硫代硫酸盐作为电子受体[52]，因为菌体内硫代硫酸盐还原酶(thiosulfate reductase, Tsr)的存在，可以跨越硫代硫酸盐还原的第一步能量消耗反应，而直接将硫代硫酸盐还原生成亚硫酸盐进而再产生H2S[53]。
2.2 RSS的生成RSS在细胞信号传导、氧化还原的稳态调节和代谢调节中发挥着重要作用[19, 54] (图 5A)，目前也已经发现了多个RSS的内源生成途径(图 5B)。细胞中RSS主要来源于CSE和CBS催化L-胱氨酸产生半胱氨酸过硫化物(Cys-SSH)、硫醌氧化还原酶(sulfide: quinone oxidoreductase, SQR)以及超氧化物歧化酶(superoxide dismutase, SOD)氧化H2S等途径。
|
| 图 5 RSS的生理作用[23]及其生成途径示意图[55] Figure 5 Physiological functions of RSS in microorganisms and a schematic diagram illustrating the pathway for RSS generation. A: Biological reactivity of RSS. Regulation of oxidative stress and redox signaling by reactive persulfide species. Excess production of ROS and NO causes oxidative stress. In contrast, ROS and NO also function as redox signals via formation of electrophilic second messengers such as 8-nitro-cGMP[23]. B: Pathways for bacterial sulfur transformation in the periplasm. Oxidation of S2− and S0: Flavocyt c sulfide dehydrogenases (FCSDs) can oxidize H2S to the final product polysulfide. In dissimilatory sulfur-oxidizing bacteria, Rhds and PDOs are located in the periplasm, and the oxidation of H2S is catalyzed by SQRs, which consistently expose the reaction to the periplasm space. Oxidation of S0 and S2+: Unconjugated SoxYZ is catalyzed by SoxAX with S2O32−, generating SoxYZ-S-S-SO3−, which is subsequently converted to SoxYZ-S-S−, releasing one molecular of SO42− under the catalysis of SoxB[55]. |
2.2.1 3-MST
3-MST能够以Trx作为硫受体产生多硫化物和H2S，第一步是硫代硫酸盐或三巯基丙酮酸上的多个硫原子转移到E. coli 3-MST的第247位半胱氨酸上，第二步硫原子转移到还原型的Trx的32位半胱氨酸上；第三步是Trx上的32位半胱氨酸与35位半胱氨酸被氧化形成二硫键，接着多硫化物被释放出来。被氧化的Trx再被Trx还原酶(thioredoxin reductase, TrxR)和NADPH还原重新利用，此过程消耗了NADPH[27]。此外，动物细胞中3-MST也可催化其底物3-MP，产生中间产物3-MST-SnSH，该中间产物能够被降解为H2Sn，H2Sn再将硫原子转移到其他硫醇(Cys、GSH等)上从而形成过硫化物(Cys-SSH等)或该中间产物直接将硫原子转移到其他硫醇或H2S上[55-56]。
2.2.2 CBS和CSE在哺乳动物组织中，CBS和CSE作为转硫途径的关键酶，可以以胱氨酸作为底物通过β-消除反应产生半胱氨酸过硫化物(Cys-SSH)、丙酮酸和氨，以半胱氨酸作为底物产生H2S。通过Cys-SSH与谷胱甘肽(glutathione, GSH)或蛋白质半胱氨酸硫醇的进一步交换反应，可以形成各自的过硫化物(GSSH和蛋白质过硫化物)，但是由于胞内的还原性环境，胱氨酸浓度远低于半胱氨酸，因此在生理条件下相比于H2S的产生，CBS和CSE催化的Cys-SSH生成量较低，其中CSE催化生成Cys-SSH的活性是CBS的20倍，同时CSE还能催化同型胱氨酸产生同型半胱氨酸过硫化物[45]。
2.2.3 SQRSQR属于谷胱甘肽还原酶家族，广泛分布于自养和异养细菌中。SQR是一种膜蛋白，依赖其表面的黄素腺嘌呤二核苷酸(flavin adenine dinucleotide, FAD)催化H2S中的硫生成零价硫(S0)，其过程为H2S中的硫将脱下的电子转移给细胞膜上的辅酶Q或甲基奈醌，再通过呼吸链传递给氧，最后生成S0。S0在有合适受体(如GSH)和下游酶(如PDO)时，会形成GSSH进而被PDO氧化为亚硫酸盐；在无合适受体时则结合在SQR的保守性半胱氨酸残基上，形成SQR-S-S中间体，并随着H2S的多轮氧化而逐渐加长，直到形成S8环，从SQR上脱落下来，从而胞内积累单质硫[58] (图 5B)。
2.2.4 硫氧化系统无机硫、硫化物等能够通过黄素细胞色素c-硫化物脱氢酶(flavocyt c sulfide dehydrogenases, FCSDs)、胞质铜/锌超氧化物歧化酶(superoxide dismutase, SOD)以及硫磺氧化系统(sulfur oxidizing system, SOX)氧化成RSS (图 5B)。FCSDs是硫氧化细菌中呼吸链的中心酶之一[59-61]，由一个大的硫化物结合蛋白(FccB)和一个小的细胞色素c (FccA)组成，能够将细菌中的硫化物氧化为RSS[62-63]，其主要存在于光合硫氧化细菌和化能无机硫氧化细菌中，分布不如SQR广泛[64]。在泛养副球菌(Paracoccus pantotrophus)及其他细菌中，fccA和fccB的同源基因常被称为soxE和soxF，通常fccA和fccB会与其他参与硫代硫酸盐氧化的sox基因聚集在一起，然而在绿硫细菌(green sulfur bacteria, GSB)中这种聚集现象并不发生[65]。钩虫贪铜菌(Cupriavidus necator) H16在没有SQR的情况下通过FCSDs氧化硫化物，FCSDs与PDO结合类似于SQR-PDO途径，将硫化物氧化为亚硫酸盐和硫代硫酸盐[60]。SOD能够催化H2S氧化产生硫烷，还能够代谢硫化物以及催化超氧化物歧化为氧和过氧化氢。SOD的H2S代谢可能是使硫化物解毒或调节RSS的古老机制。SOX系统是一套完整的硫氧化系统，主要由周质空间中的SoxYZ、SoxAX、SoxB和Sox(CD)2构成，能够通过氧化硫代硫酸盐、硫化物等含硫无机化合物，产生硫酸盐，同时根据文献[66]报道，H2S进入SOX系统是在氧化态SoxXA的辅助下进行的，H2S先与SoxYZ的SoxY上的半胱氨酸残基结合，形成SoxZY-S-S−，之后进入正常的代谢，由SoxCD脱氢氧化硫烷形成SoxZY-S-SO3−，再由SoxB水解形成SO42−。然而，在贪铜菌(Cupriavidus pinatubonensis) JMP134中包含一个完整的Sox系统，敲除soxCD后，PDO和H2S释放在减轻RSS毒性方面起着关键作用[67]。
3 硫稳态调控机制RSS是一种潜在的重要信号和效应分子，通过维持胞内氧化压力[68]及影响蛋白活性[69]进而来维持细胞生理平衡，但是高浓度的RSS在生物体内具有毒害作用[70]。因此，细胞内的RSS浓度受到严谨调控并保持在一定范围内[71] (图 6)。RSS传感器在细菌中广泛存在，其能够调节内源H2S及RSS的产生从而达到H2S/RSS平衡。例如，来自金黄色葡萄球菌(Staphylococcus aureus)[73]和粪肠球菌(Enterococcus faecalis)中的CstR[74]、来自红荚膜红杆菌(Rhodobacter capsulatus)的SqrR[75]、来自鲍曼不动杆菌(Acinetobacter baumannii)的BigR[76]、来自C. pinatubonensis的FisR[77-79]以及来自E. coli的OxyR[28, 80-81]等。
3.1 OxyR
OxyR是一个全局转录调控因子，它可以感应氧化压力的变化，同时也可以响应RSS。
(图 7A)。OxyR的C199和C208是2个可以感应ROS的半胱氨酸残基，在氧化压力下，C199首先会被氧化成Cys-SOH，再与C208脱水形成二硫键[80]，同时OxyR的氧化状态是可逆的，DTT等还原剂可以将其还原。在C199形成Cys-SOH或C199与C208形成二硫键后，受OxyR控制的下游基因trxC、grxA、katG开始转录。H2Sn能够修饰OxyR形成OxyR-SSH，进而激活Trx和谷氧还蛋白(glutaredoxin, Grx)的表达，将RSS还原成H2S[81]。在E. coli中OxyR的缺失会使胞内RSS浓度上升，E. coli对RSS的胁迫更敏感，RSS通过激活E. coli中TrxC、GrxA以及KatG的表达降低胞内RSS浓度，使E. coli胞内RSS的浓度控制在正常范围内[28]。
|
| 图 7 微生物RSS传感器的调节操作子、调节方式、结构和RSS反应产物[72] Figure 7 Regulated operons, modes of regulation, structure, and RSS reactivity products of bacterial RSS sensors. A: The expression of GrxA, TrxC, and KatG (catalase) is regulated by OxyR upon exposure to H2O2. B: CstR has four peripheral dithiol-sensing sites in the tetrameric structure (middle). The reaction products of CstR with RSS reveal a mixture of di-, tri-, and tetrasulfide interprotomer linkages[72]. C: FisR isσ54-dependent transcriptional activator and activates the expression of a sulfide detoxification operon. FisR is organized into three domains (regulatory, ATPase, and DNA-binding domain), but to date, there are no structures of a functionally characterized RSS-sensing FisR (middle)[72]. |
3.2 CstR
CstR是转录阻遏物CsoR (铜敏感操纵子阻遏物)家族的成员，最早在S. aureus中发现[82] (图 7B)。S. aureus中的CstR通过过硫化物中间体将硫化物氧化成硫代硫酸盐。CstR由88个氨基酸组成，包含2个半胱氨酸残基(C31和C60)，可以感受外界的RSS信号。cst操纵子是由外源性细胞硫化物胁迫瞬时诱导的，cst编码的蛋白CstR被认为是可以清除细胞中应激升高的低过硫化物(low persulfide, LMW)，其既能感知无机(多)硫化物，也能感知LMW硫醇的有机过硫化物，并在C31和C60之间形成二硫化物、三硫化物和四硫化物的混合物。由cst操纵子控制的基因包括cstA、cstB和sqr，能够减轻细胞硫化物毒性的影响。通常CstR结合在启动子上游的调控区，而RSS能修饰CstR上的半胱氨酸残基，使C31和C60之间形成二、三、四硫键发生构象改变，阻止CstR与cst操纵子的结合，解除对下游硫代谢相关基因的抑制[83]，因此在RSS存在的情况下，CstR被RSS修饰后，从操纵子上释放下来。
3.3 FisR来源于Cupriavidus pinatubonensis JMP134的FisR是一类增强子蛋白，具有增强子蛋白的典型结构(图 7C)，该蛋白内部分有R结构域和D结构域，R结构域的3个半胱氨酸残基是感应RSS调控的关键位点，D结构域可以和启动子上游序列结合[77]。FisR调控2个关键的硫化物氧化基因sqr和pdo，二者能够共同将硫化物氧化为多硫化物、亚硫酸盐和硫代硫酸盐，RSS作用于FisR上的2个保守的半胱氨酸残基C53和C64，使之同时形成二硫键和四硫键，FisR构象的改变引起了ATP水解酶活性改变，激活启动子，增强PDO和SQR的表达量，加速硫化物氧化[78]。FisR感应多硫化物后，自身会激活从而提高下游硫氧化操纵子基因的表达水平，增强硫耐受性。通过FisR转录因子的GFP报告系统的构建，发现多硫化物是FisR表达的直接诱导物。在硫化物或多硫化物浓度升高时，FisR可以迅速响应，产生ATP酶活，因此，整个“转录-激活过程”始终保持一个“待命状态”，以确保C. pinatubonensis JMP134对硫化物产生快速应答[79]。
4 蛋白过硫化修饰在生物学合成中的应用微生物合成L-半胱氨酸的过程与过硫化修饰密切相关，通过对L-半胱氨酸代谢、过硫化修饰、氧化应激间的调控机制解析，不但有助于了解上述生理过程的生物学意义，对含硫氨基酸的代谢改造也有重要指导意义。H2S在水溶液中以H2S、HS−、S2−形式存在，其中S2−能够在CysK的催化下重新生成L-半胱氨酸，L-半胱氨酸通过CAT/MST转化成RSS，H2O2可以氧化RSS为硫代硫酸盐，同时在氧气的存在下S2−容易发生氧化形成RSS[84]，硫代硫酸硫转移酶(thiosulfate sulfurtransferase, PspE)会催化硫代硫酸盐中硫的转移从而形成一种酶-硫中间体[85] (图 8)。通过对CstB、Sqr代谢调控机制的解析，Du等在谷氨酸棒杆菌(Corynebacterium glutamicum)中成功将H2S转化为硫代硫酸盐，实现硫的再利用[87]；Zhang等通过对硫途径的进一步强化策略使硫利用率达到52.8%[88]，但CDs能够将L-半胱氨酸降解成H2S导致硫利用率降低；Huang等通过对碳硫模块的协同表达显著提升了甲硫氨酸的产量[89]；同时对菌株提供不同的硫源也会影响其本身的状态，Huang等在培养基中添加硫代硫酸钠使甲硫氨酸产量提高了11.45%[90]。
|
| 图 8 Escherichia coli中H2S和RSS产生的模型 Figure 8 Model of Escherichia coli production of H2S and RSS. CDs convert L-cysteine to H2S. Most of the produced H2S is lost via evaporating, the rest of the hydrogen sulfide is used by CysK and CysM to produce L-cysteine[86]. H2O2 can oxidize reactive sulfane sulfur to thiosulfate[46]. Sqr and CstB can use H2S to produce thiosulfonate[87]. CAT/MST metabolizes L-cysteine to produce reactive sulfur, which causes protein sulfhydrating. Cellular mercaptans and thioredoxin/pentadidoxin reduce excess active sulfathionate to H2S, but this is not an efficient way to produce H2S during normal growth. |
5 研究展望
本文综述了蛋白质过硫化修饰的形成过程及细菌内的硫稳态调控机制，不仅有助于了解H2S、RSS生成机制，而且进一步阐述了H2S和RSS之间的联系及细菌内硫稳态调控的机制。然而在对过硫化修饰研究中还存在以下问题：(1) 在细胞内RSS种类繁多且有着复杂的转换关系，因此在微生物内硫的转化和代谢过程中实现对胞内RSS水平实时、动态、精确的检测对于过硫化修饰来说十分重要；(2) 其次过硫化修饰可能会受到环境中氧化还原条件等的影响，蛋白中存在着多个潜在的过硫化修饰位点，每个位点都可能改变蛋白质的结构和功能，最终导致蛋白质的结构功能差异，若经过过硫化修饰的半胱氨酸残基在蛋白质结构和功能的关键区域外则是无效过硫化；(3) 维持硫稳态的潜在机制仍不明确[5]等原因导致过硫化修饰的研究仍处于发展阶段；(4) 在微生物及动植物体内蛋白质的半胱氨酸残基除了能够发生过硫化修饰之外，硫原子还能与氮、氧原子形成氮氧硫桥(−N−O−S−)[91]，因此半胱氨酸残基及硫原子不仅与过硫化修饰相关，还存在着与其他原子的相互作用，其中复杂的作用关系还需要进一步探索。因此通过详细介绍蛋白质过硫化修饰机制及其在代谢工程中的应用，提出以下几点展望：(1) 微生物合成L-半胱氨酸的过程与过硫化修饰密切相关，通过对半胱氨酸代谢、过硫化修饰、氧化应激间的调控机制解析，不但有助于了解上述生理过程的生物学意义，对含硫氨基酸的代谢改造也有重要指导意义；(2) 蛋白质中半胱氨酸残基上的硫原子除了形成二硫桥外，还能与其他氨基酸形成共价交联，例如半胱氨酸-赖氨酸残基之间的氮氧硫桥，这些新结构的发现对蛋白质的功能结构有了更深入的了解，因此硫原子与其他原子之间的相互作用、半胱氨酸残基与其他氨基酸残基之间的作用关系也值得进一步探索；(3) 蛋白质过硫化的检测技术仍需要进一步发展。
| [1] | CHEN L, KASHINA A. Post-translational modifications of the protein termini[J]. Frontiers in Cell and Developmental Biology, 2021, 9: 719590 DOI:10.3389/fcell.2021.719590. |
| [2] | VALBERG SJ, PERUMBAKKAM S, McKENZIE EC, FINNO CJ. Proteome and transcriptome profiling of equine myofibrillar myopathy identifies diminished peroxiredoxin 6 and altered cysteine metabolic pathways[J]. Physiological Genomics, 2018, 50(12): 1036-1050 DOI:10.1152/physiolgenomics.00044.2018. |
| [3] | WANG LJ, MU XJ, CHEN X, HAN Y. Hydrogen sulfide attenuates intracellular oxidative stress via repressing glycolate oxidase activities in Arabidopsis thaliana[J]. BMC Plant Biology, 2022, 22(1): 98 DOI:10.1186/s12870-022-03490-3. |
| [4] | SUN HJ, WU ZY, NIE XW, BIAN JS. Role of hydrogen sulfide and polysulfides in neurological diseases: focus on protein S-persulfidation[J]. Current Neuropharmacology, 2021, 19(6): 868-884. |
| [5] | LIN VS, CHEN W, XIAN M, CHANG CJ. Chemical probes for molecular imaging and detection of hydrogen sulfide and reactive sulfur species in biological systems[J]. Chemical Society Reviews, 2015, 44(14): 4596-4618 DOI:10.1039/C4CS00298A. |
| [6] | HE B, ZHANG Z, HUANG Z, DUAN XR, WANG Y, CAO JJ, LI L, HE K, NICE EC, HE WF, GAO W, SHEN ZS. Protein persulfidation: rewiring the hydrogen sulfide signaling in cell stress response[J]. Biochemical Pharmacology, 2023, 209: 115444 DOI:10.1016/j.bcp.2023.115444. |
| [7] | HOLZEROVÁ E, PROKISCH H. Mitochondria: much ado about nothing? How dangerous is reactive oxygen species production?[J]. The International Journal of Biochemistry & Cell Biology, 2015, 63: 16-20. |
| [8] | PAUL BD, SNYDER SH. Gasotransmitter hydrogen sulfide signaling in neuronal health and disease[J]. Biochemical Pharmacology, 2018, 149: 101-109 DOI:10.1016/j.bcp.2017.11.019. |
| [9] | PARK CM, WEERASINGHE L, DAY JJ, FUKUTO JM, XIAN M. Persulfides: current knowledge and challenges in chemistry and chemical biology[J]. Molecular BioSystems, 2015, 11(7): 1775-1785 DOI:10.1039/C5MB00216H. |
| [10] | WEDMANN R, ONDERKA C, WEI SW, SZIJÁRTÓ IA, MILJKOVIC JL, MITROVIC A, LANGE MK, SAVITSKY S, YADAV PK, TORREGROSSA R, HARRER EG, HARRER T, ISHII I, GOLLASCH M, WOOD ME, GALARDON E, XIAN M, WHITEMAN M, BANERJEE R, FILIPOVIC MR. Improved tag-switch method reveals that thioredoxin acts as depersulfidase and controls the intracellular levels of protein persulfidation[J]. Chemical Science, 2016, 7(5): 3414-3426 DOI:10.1039/C5SC04818D. |
| [11] | ONO K, AKAIKE T, SAWA T, KUMAGAI Y, WINK DA, TANTILLO DJ, HOBBS AJ, NAGY P, XIAN M, LIN J, FUKUTO JM. Redox chemistry and chemical biology of H2S, hydropersulfides, and derived species: implications of their possible biological activity and utility[J]. Free Radical Biology and Medicine, 2014, 77: 82-94 DOI:10.1016/j.freeradbiomed.2014.09.007. |
| [12] | ABE K, KIMURA H. The possible role of hydrogen sulfide as an endogenous neuromodulator[J]. The Journal of Neuroscience, 1996, 16(3): 1066-1071 DOI:10.1523/JNEUROSCI.16-03-01066.1996. |
| [13] | YANG H, ZHANG B, WU ZD, CHEN LF, PAN JY, XIU XL, CAI X, LIU ZQ, ZHENG YG. Combinatorial metabolic engineering of Escherichia coli for enhanced L-cysteine production: insights into crucial regulatory modes and optimization of carbon-sulfur metabolism and cofactor availability[J]. Journal of Agricultural and Food Chemistry, 2023, 71(36): 13409-13418 DOI:10.1021/acs.jafc.3c03709. |
| [14] | OLSON KR. Are reactive sulfur species the new reactive oxygen species?[J]. Antioxidants & Redox Signaling, 2020, 33(16): 1125-1142. |
| [15] | MIRONOV A, SEREGINA T, SHATALIN K, NAGORNYKH M, SHAKULOV R, NUDLER E. CydDC functions as a cytoplasmic cystine reductase to sensitize Escherichia coli to oxidative stress and aminoglycosides[J]. Proceedings of the National Academy of Sciences of the United States of America, 2020, 117(38): 23565-23570. |
| [16] | OHTSU I, WIRIYATHANAWUDHIWONG N, MORIGASAKI S, NAKATANI T, KADOKURA H, TAKAGI H. The L-cysteine/L-cystine shuttle system provides reducing equivalents to the periplasm in Escherichia coli[J]. The Journal of Biological Chemistry, 2010, 285(23): 17479-17487 DOI:10.1074/jbc.M109.081356. |
| [17] |
张玲娜, 董丽, 廖红梅. 细菌响应过量活性氧的存活策略及相关研究进展[J]. 微生物学通报, 2021, 48(4): 1249-1259.
ZHANG LN, DONG L, LIAO HM. Survival strategies of bacteria in response to excessive reactive oxygen species: a review[J]. Microbiology China, 2021, 48(4): 1249-1259 (in Chinese). |
| [18] | GERRITY S, KENNELLY C, CLIFFORD E, COLLINS G. Hydrogen sulfide oxidation in novel horizontal-flow biofilm reactors dominated by an Acidithiobacillus and a Thiobacillus species[J]. Environmental Technology, 2016, 37(17): 2252-2264 DOI:10.1080/09593330.2016.1147609. |
| [19] | POKORNA D, ZABRANSKA J. Sulfur-oxidizing bacteria in environmental technology[J]. Biotechnology Advances, 2015, 33(6): 1246-1259 DOI:10.1016/j.biotechadv.2015.02.007. |
| [20] | FILIPOVIC MR, ZIVANOVIC J, ALVAREZ B, BANERJEE R. Chemical biology of H2S signaling through persulfidation[J]. Chemical Reviews, 2018, 118(3): 1253-1337 DOI:10.1021/acs.chemrev.7b00205. |
| [21] | LI Q, JR LANCASTER JR. Chemical foundations of hydrogen sulfide biology[J]. Nitric Oxide: Biology and Chemistry, 2013, 35: 21-34 DOI:10.1016/j.niox.2013.07.001. |
| [22] | GOTOR C, GARCÍA I, AROCA Á, LAUREANO-MARÍN AM, ARENAS-ALFONSECA L, JURADO-FLORES A, MORENO I, ROMERO LC. Signaling by hydrogen sulfide and cyanide through post-translational modification[J]. Journal of Experimental Botany, 2019, 70(16): 4251-4265 DOI:10.1093/jxb/erz225. |
| [23] | FENG JN, LU XX, LI H, WANG SX. The roles of hydrogen sulfide in renal physiology and disease states[J]. Renal Failure, 2022, 44(1): 1289-1308. |
| [24] |
WANG QD. The mechanism of sulfurtransferase to maintain mitochondrial health in eukaryotic cells[D]. Jinan: Doctoral Dissertation of Shandong University, 2022 (in Chinese). 王清达. 硫转移酶维持真核细胞线粒体健康的机制研究[D]. 济南: 山东大学博士学位论文, 2022. |
| [25] | MISHANINA TV, LIBIAD M, BANERJEE R. Biogenesis of reactive sulfur species for signaling by hydrogen sulfide oxidation pathways[J]. Nature Chemical Biology, 2015, 11: 457-464 DOI:10.1038/nchembio.1834. |
| [26] | KUMAR R, BANERJEE R. Regulation of the redox metabolome and thiol proteome by hydrogen sulfide[J]. Critical Reviews in Biochemistry and Molecular Biology, 2021, 56(3): 221-235 DOI:10.1080/10409238.2021.1893641. |
| [27] | SHIBUYA N, TANAKA M, YOSHIDA M, OGASAWARA Y, TOGAWA T, ISHII K, KIMURA H. 3-mercaptopyruvate sulfurtransferase produces hydrogen sulfide and bound sulfane sulfur in the brain[J]. Antioxidants & Redox Signaling, 2009, 11(4): 703-714. |
| [28] |
HOU NK. The regulation of reactive sulfane sulfur by OxyR in E. coli and application of H2S oxidation by heterotrophic bacteria[D]. Jinan: Doctoral Dissertation of Shandong University, 2019 (in Chinese). 侯宁可. 大肠杆菌中OxyR对活性硫烷硫的调控以及异养细菌氧化硫化氢的应用研究[D]. 济南: 山东大学博士学位论文, 2019. |
| [29] | TOOHEY JI, COOPER AJL. Thiosulfoxide (sulfane) sulfur: new chemistry and new regulatory roles in biology[J]. Molecules, 2014, 19(8): 12789-12813 DOI:10.3390/molecules190812789. |
| [30] | KIMURA Y, MIKAMI Y, OSUMI K, TSUGANE M, OKA JI, KIMURA H. Polysulfides are possible H2S-derived signaling molecules in rat brain[J]. The FASEB Journal, 2013, 27(6): 2451-2457 DOI:10.1096/fj.12-226415. |
| [31] | SUN F, LUO JH, YUE TT, WANG FX, YANG CL, ZHANG S, WANG XQ, WANG CY. The role of hydrogen sulphide signalling in macrophage activation[J]. Immunology, 2021, 162(1): 3-10 DOI:10.1111/imm.13253. |
| [32] | PAUL BD, SNYDER SH. H2S signalling through protein sulfhydration and beyond[J]. Nature Reviews Molecular Cell Biology, 2012, 13: 499-507 DOI:10.1038/nrm3391. |
| [33] | MA Y, YANG XM, WANG HO, QIN ZX, YI CR, SHI CP, LUO M, CHEN GZ, YAN J, LIU XY, LIU Z. CBS-derived H2S facilitates host colonization of Vibrio cholerae by promoting the iron-dependent catalase activity of KatB[J]. PLoS Pathogens, 2021, 17(7): e1009763 DOI:10.1371/journal.ppat.1009763. |
| [34] | OLSON KR. A practical look at the chemistry and biology of hydrogen sulfide[J]. Antioxidants & Redox Signaling, 2012, 17(1): 32-44. |
| [35] | PREDMORE BL, LEFER DJ, GOJON G. Hydrogen sulfide in biochemistry and medicine[J]. Antioxidants & Redox Signaling, 2012, 17(1): 119-140. |
| [36] | DWIVEDI CM, RAGIN RC, UREN JR. Cloning, purification, and characterization of beta-cystathionase from Escherichia coli[J]. Biochemistry, 1982, 21(13): 3064-3069 DOI:10.1021/bi00256a005. |
| [37] | AWANO N, WADA M, KOHDOH A, OIKAWA T, TAKAGI H, NAKAMORI S. Effect of cysteine desulfhydrase gene disruption on L-cysteine overproduction in Escherichia coli[J]. Applied Microbiology and Biotechnology, 2003, 62(2): 239-243. |
| [38] | AWANO N, WADA M, MORI H, NAKAMORI S, TAKAGI H. Identification and functional analysis of Escherichia coli cysteine desulfhydrases[J]. Applied and Environmental Microbiology, 2005, 71(7): 4149-4152 DOI:10.1128/AEM.71.7.4149-4152.2005. |
| [39] | PEDRE B, YALWAR D, BARAYE U, SCHILLING D, LUZAROWSHI M, SOKOLOWSHI M, GLATT S, DICK TP. 3-Mercaptopyruvate sulfur transferase is a protein persulfidase[J]. Nature Chemical Biology, 2023, 19(4): 507-517 DOI:10.1038/s41589-022-01244-8. |
| [40] | SHATALIN K, SHATALINA E, MIRONOV A, NUDLER E. H2S: a universal defense against antibiotics in bacteria[J]. Science, 2011, 334(6058): 986-990 DOI:10.1126/science.1209855. |
| [41] | GADALLA MM, SNYDER SH. Hydrogen sulfide as a gasotransmitter[J]. Journal of Neurochemistry, 2010, 113(1): 14-26 DOI:10.1111/j.1471-4159.2010.06580.x. |
| [42] | SHACKELFORD RE, ABDULSATTAR J, WEI EX, COTELINGAM J, COPPOLA D, HERRERA GA. Increased nicotinamide phosphoribosyltransferase and cystathionine-β-synthase in renal oncocytomas, renal urothelial carcinoma, and renal clear cell carcinoma[J]. Anticancer Research, 2017, 37(7): 3423-3427. |
| [43] | SINGH S, PADOVANI D, LESLIE RA, CHIKU T, BANERJEE R. Relative contributions of cystathionine beta-synthase and gamma-cystathionase to H2S biogenesis via alternative trans-sulfuration reactions[J]. The Journal of Biological Chemistry, 2009, 284(33): 22457-22466 DOI:10.1074/jbc.M109.010868. |
| [44] | KABIL O, BANERJEE R. Enzymology of H2S biogenesis, decay and signaling[J]. Antioxidants & Redox Signaling, 2014, 20(5): 770-782. |
| [45] | YADAV PK, MARTINOV M, VITVITSKY V, SERAVALLI J, WEDMANN R, FILIPOVIC MR, BANERJEE R. Biosynthesis and reactivity of cysteine persulfides in signaling[J]. Journal of the American Chemical Society, 2016, 138(1): 289-299 DOI:10.1021/jacs.5b10494. |
| [46] | MIRONOV A, SEREGINA T, NAGORNYKH M, LUHACHACK LG, KOROLKOVA N, LOPES LE, KOTOVA V, ZAVILGELSKY G, SHAKULOV R, SHATALIN K, NUDLER E. Mechanism of H2S-mediated protection against oxidative stress in Escherichia coli[J]. Proceedings of the National Academy of Sciences of the United States of America, 2017, 114(23): 6022-6027. |
| [47] | KIMURA H, SHIBUYA N, KIMURA Y. Hydrogen sulfide is a signaling molecule and a cytoprotectant[J]. Antioxidants & Redox Signaling, 2012, 17(1): 45-57. |
| [48] | STIPANUK MH. Sulfur amino acid metabolism: pathways for production and removal of homocysteine and cysteine[J]. Annual Review of Nutrition, 2004, 24: 539-577 DOI:10.1146/annurev.nutr.24.012003.132418. |
| [49] | STIPANUK MH, BECK PW. Characterization of the enzymic capacity for cysteine desulphhydration in liver and kidney of the rat[J]. The Biochemical Journal, 1982, 206(2): 267-277 DOI:10.1042/bj2060267. |
| [50] | ANANDKUMAR B, GEORGE RP, MARUTHAMUTHU S, PARVATHAVARTHINI N, MUDALI UK. Corrosion characteristics of sulfate-reducing bacteria (SRB) and the role of molecular biology in SRB studies: an overview[J]. Corrosion Reviews, 2016, 34(1/2): 41-63. |
| [51] | MÜLLER AL, KJELDSEN KU, RATTEI T, PESTER M, LOY A. Phylogenetic and environmental diversity of DsrAB-type dissimilatory (bi)sulfite reductases[J]. The ISME Journal, 2015, 9(5): 1152-1165 DOI:10.1038/ismej.2014.208. |
| [52] |
LU T. The mechanism of sulfane sulfur regulating secondary metabolism and differentiation in Streptomyces coelicolor[D]. Jinan: Doctoral Dissertation of Shandong University, 2022 (in Chinese). 卢婷. 硫烷硫在天蓝色链霉菌次级代谢和分化发育过程中的调控机制研究[D]. 济南: 山东大学博士学位论文, 2022. |
| [53] | AKETAGAWA J, KOBAYASHI K, ISHIMOTO M. Purification and properties of thiosulfate reductase from Desulfovibrio vulgaris, Miyazaki F[J]. Journal of Biochemistry, 1985, 97(4): 1025-1032 DOI:10.1093/oxfordjournals.jbchem.a135144. |
| [54] | GRUHLKE MCH, SLUSARENKO AJ. The biology of reactive sulfur species (RSS)[J]. Plant Physiology and Biochemistry, 2012, 59: 98-107 DOI:10.1016/j.plaphy.2012.03.016. |
| [55] | HAN SR, LI YX, GAO HC. Generation and physiology of hydrogen sulfide and reactive sulfur species in bacteria[J]. Antioxidants, 2022, 11(12): 2487 DOI:10.3390/antiox11122487. |
| [56] | LIU H, RADFORD MN, YANG CT, CHEN W, XIAN M. Inorganic hydrogen polysulfides: chemistry, chemical biology and detection[J]. British Journal of Pharmacology, 2019, 176(4): 616-627 DOI:10.1111/bph.14330. |
| [57] | KHARMA A, GRMAN M, MISAK A, DOMÍNGUEZ-ÁLVAREZ E, NASIM MJ, ONDRIAS K, CHOVANEC M, JACOB C. Inorganic polysulfides and related reactive sulfur-selenium species from the perspective of chemistry[J]. Molecules, 2019, 24(7): 1359 DOI:10.3390/molecules24071359. |
| [58] | CHERNEY MM, ZHANG YF, SOLOMONSON M, WEINER JH, JAMES MNG. Crystal structure of sulfide: quinone oxidoreductase from Acidithiobacillus ferrooxidans: insights into sulfidotrophic respiration and detoxification[J]. Journal of Molecular Biology, 2010, 398(2): 292-305 DOI:10.1016/j.jmb.2010.03.018. |
| [59] | LÜ CJ, XIA YZ, LIU DX, ZHAO R, GAO R, LIU HL, XUN LY. Cupriavidus necator H16 uses flavocytochrome c sulfide dehydrogenase to oxidize self-produced and added sulfide[J]. Applied and Environmental Microbiology, 2017, 83(22): e01610-e01617. |
| [60] | FUKUMORI Y, YAMANAKA T. Flavocytochrome c of Chromatium vinosum. Some enzymatic properties and subunit structure[J]. Journal of Biochemistry, 1979, 85(6): 1405-1414 DOI:10.1093/oxfordjournals.jbchem.a132467. |
| [61] | VISSER JM, de JONG GAH, ROBERTSON LA, KUENEN JG. A novel membrane-bound flavocytochrome c sulfide dehydrogenase from the colourless sulfur bacterium Thiobacillus sp. W5[J]. Archives of Microbiology, 1997, 167(5): 295-301 DOI:10.1007/s002030050447. |
| [62] | XIA YZ, LÜ CJ, HOU NK, XIN YF, LIU JH, LIU HL, XUN LY. Sulfide production and oxidation by heterotrophic bacteria under aerobic conditions[J]. The ISME Journal, 2017, 11(12): 2754-2766 DOI:10.1038/ismej.2017.125. |
| [63] | KOSTANJEVECKI V, BRIGÉ A, MEYER TE, CUSANOVICH MA, GUISEZ Y, van BEEUMEN J. A membrane-bound flavocytochrome c-sulfide dehydrogenase from the purple phototrophic sulfur bacterium Ectothiorhodospira vacuolata[J]. Journal of Bacteriology, 2000, 182(11): 3097-3103 DOI:10.1128/JB.182.11.3097-3103.2000. |
| [64] |
胡欣, 刘纪化, 刘怀伟, 庄光超, 荀鲁盈. 异养细菌硫代谢及其在海洋硫循环中的作用[J]. 中国科学: 地球科学, 2018, 48(12): 1540-1550.
HU X, LIU JH, LIU HW, ZHUANG GC, XUN LY. Sulfur metabolism by marine heterotrophic bacteria involved in sulfur cycling in the ocean[J]. Scientia Sinica (Terrae), 2018, 48(12): 1540-1550 (in Chinese). |
| [65] | GREGERSEN LH, BRYANT DA, FRIGAARD NU. Mechanisms and evolution of oxidative sulfur metabolism in green sulfur bacteria[J]. Frontiers in Microbiology, 2011, 2: 116. |
| [66] | CHEN LX, REN YL, LIN JQ, LIU XM, PANG X, LIN JQ. Acidithiobacillus caldus sulfur oxidation model based on transcriptome analysis between the wild type and sulfur oxygenase reductase defective mutant[J]. PLoS One, 2012, 7(9): e39470 DOI:10.1371/journal.pone.0039470. |
| [67] | XIN YF, WANG YX, ZHANG HL, WU Y, XIA YZ, LI HJ, QU XH. Cupriavidus pinatubonensis JMP134 alleviates sulfane sulfur toxicity after the loss of sulfane dehydrogenase through oxidation by persulfide dioxygenase and hydrogen sulfide release[J]. Metabolites, 2023, 13(2): 218 DOI:10.3390/metabo13020218. |
| [68] | IDA T, SAWA T, IHARA H, TSUCHIYA Y, WATANABE Y, KUMAGAI Y, SUEMATSU M, MOTOHASHI H, FUJII S, MATSUNAGA T, YAMAMOTO M, ONO K, DEVARIE-BAEZ NO, XIAN M, FUKUTO JM, AKAIKE T. Reactive cysteine persulfides and S-polythiolation regulate oxidative stress and redox signaling[J]. Proceedings of the National Academy of Sciences of the United States of America, 2014, 111(21): 7606-7611. |
| [69] | PAUL BD, SNYDER SH. Protein sulfhydration[J]. Methods in Enzymology, 2015, 555: 79-90. |
| [70] | XU ZB, QIU ZY, LIU Q, HUANG YX, LI DD, SHEN XG, FAN KL, XI JQ, GU YH, TANG Y, JIANG J, XU JL, HE JZ, GAO XF, LIU Y, KOO H, YAN XY, GAO LZ. Converting organosulfur compounds to inorganic polysulfides against resistant bacterial infections[J]. Nature Communications, 2018, 9: 3713 DOI:10.1038/s41467-018-06164-7. |
| [71] | LU T, CAO Q, PANG XH, XIA YZ, XUN LY, LIU HW. Sulfane sulfur-activated actinorhodin production and sporulation is maintained by a natural gene circuit in Streptomyces coelicolor[J]. Microbial Biotechnology, 2020, 13(6): 1917-1932 DOI:10.1111/1751-7915.13637. |
| [72] | WALSH BJC, GIEDROC DP. H2S and reactive sulfur signaling at the host-bacterial pathogen interface[J]. Journal of Biological Chemistry, 2020, 295(38): 13150-13168 DOI:10.1074/jbc.REV120.011304. |
| [73] | GROSSOEHME N, KEHL-FIE TE, MA Z, ADAMS KW, COWART DM, SCOTT RA, SKAAR EP, GIEDROC DP. Control of copper resistance and inorganic sulfur metabolism by paralogous regulators in Staphylococcus aureus[J]. The Journal of Biological Chemistry, 2011, 286(15): 13522-13531 DOI:10.1074/jbc.M111.220012. |
| [74] | SHEN JC, WALSH BJC, FLORES-MIRELES AL, PENG H, ZHANG YF, ZHANG YX, TRINIDAD JC, HULTGREN SJ, GIEDROC DP. Hydrogen sulfide sensing through reactive sulfur species (RSS) and nitroxyl (HNO) in Enterococcus faecalis[J]. ACS Chemical Biology, 2018, 13(6): 1610-1620 DOI:10.1021/acschembio.8b00230. |
| [75] | SHIMIZU T, SHEN JC, FANG MX, ZHANG YX, HORI K, TRINIDAD JC, BAUER CE, GIEDROC DP, MASUDA S. Sulfide-responsive transcriptional repressor SqrR functions as a master regulator of sulfide-dependent photosynthesis[J]. Proceedings of the National Academy of Sciences of the United States of America, 2017, 114(9): 2355-2360. |
| [76] | BARBOSA RL, BENEDETTI CE. BigR, a transcriptional repressor from plant-associated bacteria, regulates an operon implicated in biofilm growth[J]. Journal of Bacteriology, 2007, 189(17): 6185-6194. |
| [77] |
LI J. Study on the regulation of Fis family regulators in Cupriavidus pinatubbonensis JMP 134 on sulfide oxidation pathway[D]. Jinan: Master's Thesis of Shandong University, 2016 (in Chinese). 李娟. Cupriavidus pinatubonensis JMP134中Fis家族调控子对硫化物氧化途径的调控作用研究[D]. 济南: 山东大学硕士学位论文, 2016. |
| [78] | LI HJ, LI J, LÜ CJ, XIA YZ, XIN YF, LIU HL, XUN LY, LIU HW. FisR activates σ54-dependent transcription of sulfide-oxidizing genes in Cupriavidus pinatubonensis JMP134[J]. Molecular Microbiology, 2017, 105(3): 373-384. |
| [79] |
LI HJ. Study on fluorescence characteristics and physiological function of active thioalkyl sulfur[D]. Jinan: Doctoral Dissertation of Shandong University, 2019 (in Chinese). 李焕杰. 活性硫烷硫的荧光特性及生理功能研究[D]. 济南: 山东大学博士学位论文, 2019. |
| [80] | ZHENG M, ASLUND F, STORZ G. Activation of the OxyR transcription factor by reversible disulfide bond formation[J]. Science, 1998, 279(5357): 1718-1721. |
| [81] | HOU NK, YAN ZZ, FAN KL, LI HJ, ZHAO R, XIA YZ, XUN LY, LIU HW. OxyR senses sulfane sulfur and activates the genes for its removal in Escherichia coli[J]. Redox Biology, 2019, 26: 101293. |
| [82] | LIU T, RAMESH A, MA Z, WARD SK, ZHANG LM, GEORGE GN, TALAAT AM, SACCHETTINI JC, GIEDROC DP. CsoR is a novel Mycobacterium tuberculosis copper-sensing transcriptional regulator[J]. Nature Chemical Biology, 2007, 3: 60-68. |
| [83] | LUEBKE JL, SHEN JC, BRUCE KE, KEHL-FIE TE, PENG H, SKAAR EP, GIEDROC DP. The CsoR-like sulfurtransferase repressor (CstR) is a persulfide sensor in Staphylococcus aureus[J]. Molecular Microbiology, 2014, 94(6): 1343-1360. |
| [84] | ALPER E, OZTURK S. Kinetics of oxidation of aqueous sodium sulphide solutions by gaseous oxygen in a stirred cell reactor[J]. Chemical Engineering Communications, 1985, 36(1/2/3/4/5/6): 343-349. |
| [85] | CHENG H, DONAHUE JL, BATTLE SE, RAY WK, LARSON TJ. Biochemical and genetic characterization of PspE and GlpE, two single-domain sulfurtransferases of Escherichia coli[J]. The Open Microbiology Journal, 2008, 2: 18-28. |
| [86] | LI K, XIN YF, XUAN GH, ZHAO R, LIU HW, XIA YZ, XUN LY. Escherichia coli uses separate enzymes to produce H2S and reactive sulfane sulfur from L-cysteine[J]. Frontiers in Microbiology, 2019, 10: 298. |
| [87] | DU HM, QIAO JF, QI YT, LI LC, XU N, SHAO L, WEI L, LIU J. Reprogramming the sulfur recycling network to improve L-cysteine production in Corynebacterium glutamicum[J]. Green Chemistry, 2023, 25(8): 3152-3165. |
| [88] | ZHANG B, YANG H, WU ZD, PAN JY, LI SR, CHEN LF, CAI X, LIU ZQ, ZHENG YG. Spatiotemporal gene expression by a genetic circuit for chemical production in Escherichia coli[J]. ACS Synthetic Biology, 2023, 12(3): 768-779. |
| [89] | HUANG JF, SHEN ZY, MAO QL, ZHANG XM, ZHANG B, WU JS, LIU ZQ, ZHENG YG. Systematic analysis of bottlenecks in a multibranched and multilevel regulated pathway: the molecular fundamentals of L-methionine biosynthesis in Escherichia coli[J]. ACS Synthetic Biology, 2018, 7(11): 2577-2589. |
| [90] | HUANG JF, LIU ZQ, JIN LQ, TANG XL, SHEN ZY, YIN HH, ZHENG YG. Metabolic engineering of Escherichia coli for microbial production of L-methionine[J]. Biotechnology and Bioengineering, 2017, 114(4): 843-851. |
| [91] | WENSIEN M, von PAPPENHEIM FR, FUNK LM, KLOSKOWSKI P, CURTH U, DIEDERICHSEN U, URANGA J, YE J, FANG P, PAN KT, URLAUB H, MATA RA, SAUTNER V, TITTMANN K. A lysine-cysteine redox switch with an NOS bridge regulates enzyme function[J]. Nature, 2021, 593: 460-464. |