Doctor of Philosophy (PhD)


Biological Sciences

Document Type



A family of transcriptional regulators that ubiquitously exists in prokaryotes is the multiple antibiotic resistance regulator (MarR) family. These transcriptional regulators participate in many cellular processes and can provide valuable knowledge about transcriptional regulation in response to specific conditions. The closely related MarR homologs TamR (trans-aconitate methyltransferase regulator) and PecS in Streptomyces coelicolor were studied to investigate their potential role in this bacterium. In Streptomyces coelicolor, the gene (SCO3133), which encodes TamR, is oriented divergently from the tam gene, which encodes trans-aconitate methyltransferase. TamR was found to regulate several target genes, which encode several enzymes closely related to the citric acid cycle, by binding to their promoter regions. TamR can regulate the transcription of tamR (encoding TamR), tam (encoding trans-aconitate methyltransferase), sacA (encoding aconitase), aceB1 (encoding malate synthase), mdh (encoding malate dehydrogenase) and idh (encoding isocitrate dehydrogenase). Moreover, the divergent tam-tamR gene pairs and the predicted TamR binding sites are highly conserved in the promoter regions of its target genes in different Streptomyces species. Trans-aconitate can attenuate DNA-binding by TamR, as can citrate, cis-aconitate and isocitrate, which are the substrate, intermediate and product of aconitase, respectively. In vivo results also showed that citrate and hydrogen peroxide can induce upregulation of these target genes. The collected information in this study suggests that TamR plays an important and conserved role in promoting metabolic flux through the citric acid cycle under some stress conditions. S. coelicolor also encodes a PecS homolog (SCO2647) that regulates a pecM gene (SCO2646). S. coelicolor PecS, which exists as a homodimer, binds the intergenic region between pecS and pecM genes with high affinity. The binding of PecS to its target DNA can be efficiently attenuated by the ligand urate, which also quenches the intrinsic fluorescence of PecS, indicating a direct interaction between urate and PecS. In vivo measurement of gene expression showed that activity of pecS and pecM genes is significantly elevated after exposure of S. coelicolor cultures to urate. These results indicate that S. coelicolor PecS responds to the ligand urate by attenuated DNA binding in vitro and upregulation of gene activity in vivo.



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Committee Chair

Grove, Anne