TetR-family transcriptional regulators are widely distributed among bacteria and involved in various cellular processes such as multidrug and inhibitor resistance. Zymomonas mobilis is a industrial bacterium for lignocellulosic ethanol production. Although TetR-family regulators and their associated RND-family efflux pumps in Z. mobilis have been identified to be differentially expressed under various inhibitors and stressful conditions, there are no systematic investigation yet. In this study, bioinformatic analyses indicated that there are three TetR-family transcriptional regulators (ZMO0281, ZMO0963, ZMO1547) and two RND-family efflux pumps (ZMO0282-0285, ZMO0964-0966) adjacent to corresponding TetR-family regulators of ZMO0281 and ZMO0963 in Z. mobilis. Genetics studies were then carried out with various mutants of TetR-family regulators constructed, and ZMO0281 was characterized to be related to acetate tolerance. Combining transcriptomics and dual-reporter gene system, this study demonstrated that three TetR-family regulators repressed their adjacent genes specifically. Moreover, TetR-family regulator ZMO0281 might also be involved in other cellular processes in the presence of acetate. In addition, the upregulation of RND-family efflux pumps due to ZMO0281 deletion might lead to an energy imbalance and decreased cell growth in Z. mobilis under acetate stress. The systematic investigation of all three TetR-family regulators and their roles on a major lignocellulosic inhibitor acetate tolerance in Z. mobilis thus not only unravels the molecular mechanisms of TetR-family regulators and their potential cross-talks on regulating RND-family efflux pumps and other genes in Z. mobilis, but also provides guidance on understanding the roles of multiple regulators of same family in Z. mobilis and other microorganisms for efficient lignocellulosic biochemical production.

中文翻译：

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TetR 家族转录调节因子的系统研究及其对运动发酵单胞菌木质纤维素抑制剂醋酸盐耐受性的作用

TetR 家族转录调节因子广泛分布在细菌中，并参与多种细胞过程，例如多药和抑制剂耐药性。运动发酵单胞菌是一种用于生产木质纤维素乙醇的工业细菌。尽管 TetR 系列调节器及其相关的 RND 系列外排泵运动发酵杆菌已被确定在各种抑制剂和压力条件下有差异表达，但尚未进行系统研究。在这项研究中，生物信息学分析表明存在三个TetR家族转录调节因子（ZMO0281,ZMO0963,ZMO1547）和两个 RND 系列外排泵（ZMO0282-0285,ZMO0964-0966）与 ZMO0281 和 ZMO0963 的相应 TetR 系列调节器相邻运动发酵杆菌。然后对构建的 TetR 家族调节因子的各种突变体进行了遗传学研究，并ZMO0281被认为与醋酸盐耐受性有关。结合转录组学和双报告基因系统，本研究证明了三个 TetR 家族调节因子特异性抑制其邻近基因。此外，TetR 家族调节剂 ZMO0281 也可能参与醋酸盐存在下的其他细胞过程。此外，RND 系列外排泵的上调归因于ZMO0281缺失可能会导致能量不平衡和细胞生长减少运动发酵杆菌在醋酸盐胁迫下。对所有三个 TetR 家族调节剂及其对主要木质纤维素抑制剂醋酸盐耐受性的作用进行系统研究运动发酵杆菌因此，不仅揭示了 TetR 家族调节剂的分子机制及其在调节 RND 家族外排泵和其他基因中的潜在相互作用。运动发酵杆菌，而且还为理解同一家族的多个监管者的作用提供了指导运动发酵杆菌和其他微生物进行有效的木质纤维素生化生产。