Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), Wuhan University, Wuhan, People's Republic of China.
Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), Wuhan University, Wuhan, People's Republic of China
J Bacteriol. 2018 Jun 11;200(13). doi: 10.1128/JB.00087-18. Print 2018 Jul 1.
7-Hydroxytropolone (7-HT) is a symmetrical seven-membered heteroatomic ring with a carboxyl group and two hydroxyl groups and was recently reported to be an iron scavenger of HYS. Cluster 1 includes 12 genes related to the synthesis of 7-HT; among these genes, those for two regulators, Orf1 and Orf12, were predicted to regulate 7-HT biosynthesis and to be LysR-type transcriptional regulators (LTTRs) and TetR/AcrR family transcriptional regulators, respectively. Data from real-time quantitative PCR and β-galactosidase and classical siderophore assays indicated that the transcription levels of and , as well as those of crucial genes to , were repressed under high-iron conditions. The deletion of and led to an absence of 7-HT and a decrease in expression. Orf1 and Orf12 were essential for the production of 7-HT through These two regulators are regulated by the Gac/Rsm system; Orf1 facilitates the expression of Orf12, and Orf12 concomitantly stimulates the expression of to synthesize 7-HT. The overexpression of Orf12 decreased 7-HT yields, possibly through decreased expression. This work thus outlines a complex mechanism regulating the biosynthesis of the iron scavenger 7-HT in HYS. The synergy between Orf1 and Orf12 ensures that 7-HT acts as an iron chelator despite being toxic to bacteria and provides new ideas for the novel regulation of dual-functional secondary metabolism and research on 7-HT and its derivates in other bacteria. A complex regulation mechanism including two regulators, LysR and TetR/AcrR, in the biosynthesis of the novel iron scavenger 7-hydroxytropolone (7-HT) was verified in HYS. The coaction of LysR Orf1 and TetR/AcrR Orf12 may balance the toxicity and iron chelation of 7-HT in HYS to overcome iron deficiency, as well as improve the bacterial competitiveness under iron-scarce conditions because of the toxicity of 7-HT toward other bacteria, making the accurate regulation of 7-HT biosynthesis indispensable. This regulation mechanism may be ubiquitous in the group but may better explain the group's strong adaptability.
7- 羟基色酮 (7-HT) 是一种具有羧基和两个羟基的对称七元杂环，最近被报道为 HYS 的铁清除剂。簇 1 包含 12 个与 7-HT 合成相关的基因；其中，两个调节剂 Orf1 和 Orf12 的基因被预测分别调节 7-HT 生物合成和作为 LysR 型转录调节剂（LTTRs）和 TetR/AcrR 家族转录调节剂。实时定量 PCR 和 β-半乳糖苷酶和经典铁载体测定的数据表明，在高铁条件下， 和 ，以及 和 的关键基因 的转录水平受到抑制。和 的缺失导致 7-HT 缺失和 表达降低。Orf1 和 Orf12 是通过 产生 7-HT 的必要条件。这两个调节剂受 Gac/Rsm 系统调控；Orf1 促进 Orf12 的表达，而 Orf12 同时刺激 表达以合成 7-HT。Orf12 的过表达降低了 7-HT 的产量，可能是通过降低 表达。因此，这项工作概述了一个复杂的机制，调节 HYS 中铁清除剂 7-HT 的生物合成。Orf1 和 Orf12 的协同作用确保 7-HT 作为铁螯合剂发挥作用，尽管对细菌有毒，并为新型双功能次级代谢物的调控和其他细菌中 7-HT 及其衍生物的研究提供了新的思路。在 HYS 中验证了新型铁清除剂 7- 羟基色酮（7-HT）生物合成中包括两个调节剂 LysR 和 TetR/AcrR 的复杂调节机制。LysR Orf1 和 TetR/AcrR Orf12 的协同作用可能平衡了 7-HT 在 HYS 中的毒性和铁螯合作用，以克服缺铁，并且由于 7-HT 对其他细菌的毒性，提高了细菌在缺铁条件下的竞争力，使得 7-HT 生物合成的精确调节不可或缺。这种调节机制可能在 组中普遍存在，但可能更好地解释了该组的强适应性。
