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LysR-type transcriptional regulators (LTTRs) form one of the largest families of bacterial regulators. They are widely distributed and contribute to all aspects of metabolism and physiology. Most are homotetramers, with each subunit composed of an N-terminal DNA-binding domain followed by a long helix connecting to an effector-binding domain. LTTRs typically bind DNA in the presence or absence of a small-molecule ligand (effector). In response to cellular signals, conformational changes alter DNA interactions, contact with RNA polymerase, and sometimes contact with other proteins. Many are dual-function repressor–activators, although different modes of regulation may occur at multiple promoters. This review presents an update on the molecular basis of regulation, the complexity of regulatory schemes, and applications in biotechnology and medicine. The abundance of LTTRs reflects their versatility and importance. While a single regulatory model cannot describe all family members, a comparison of similarities and differences provides a framework for future study. Expected final online publication date for the Annual Review of Microbiology, Volume 77 is September 2023. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates. 

ABSTRACT Despite the significant presence of plant-derived tricarboxylic acids in some environments, few studies detail the bacterial metabolism oftrans-aconitic acid (Taa) and tricarballylic acid (Tcb). In a soil bacterium,Acinetobacter baylyiADP1, we discovered interrelated pathways for the consumption of Taa and Tcb. An intricate regulatory scheme tightly controls the transport and catabolism of both compounds and may reflect that they can be toxic inhibitors of the tricarboxylic acid cycle. The genes encoding two similar LysR-type transcriptional regulators, TcuR and TclR, were clustered on the chromosome withtcuAandtcuB, genes required for Tcb consumption. The genetic organization differed from that inSalmonella entericaserovar Typhimurium, in whichtcuAandtcuBform an operon with a transporter gene,tcuC. InA. baylyi,tcuCwas not cotranscribed withtcuAB. Rather,tcuCwas cotranscribed with a gene, designatedpacI, encoding an isomerase needed for Taa consumption. TcuC appears to transport Tcb andcis-aconitic acid (Caa), the presumed product of PacI-mediated periplasmic isomerization of Taa. Two operons,tcuC-pacIandtcuAB, were transcriptionally controlled by both TcuR and TclR, which have overlapping functions. We investigated the roles of the two regulators in activating transcription of both operons in response to multiple effector compounds, including Taa, Tcb, and Caa.IMPORTANCEIngestion of Taa and Tcb by grazing livestock can cause a serious metabolic disorder called grass tetany. The disorder, which results from Tcb absorption by ruminants, focuses attention on the metabolism of tricarboxylic acids. Additional interest stems from efforts to produce tricarboxylic acids as commodity chemicals. Improved understanding of bacterial enzymes and pathways for tricarboxylic acid metabolism may contribute to new biomanufacturing strategies.