<i>bkaR</i>is a TetR-type repressor that controls an operon associated with branched-chain keto-acid metabolism in<i>Mycobacteria</i>

Balhana, Ricardo; Swanston, Sade N.; Coade, S. B.; Withers, Mike; Sikder, Mahmudul Hasan; Stoker, Neil G.; Kendall, Sharon L.

doi:10.1111/1574-6968.12196

Cited by 15 publications

(12 citation statements)

References 27 publications

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“…The average number of binding sites for TFs with a motif was 246 (range 14–859), compared with an average of 28 peaks (range 3–437) for those TFs where a significant consensus motif could not be identified. For TFs with previously characterized DNA-binding motifs, this analysis corresponded well with previous reports (for example, Rv2506 (refs 37 , 38 ), Rv2359 (ref. 39 ), DosR (ref.…”

Section: Resultssupporting

confidence: 88%

The DNA-binding network of Mycobacterium tuberculosi s

et al. 2015

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Mycobacterium tuberculosis (MTB) infects 30% of all humans and kills someone every 20 – 30 seconds. Here we report genome-wide binding for ~80% of all predicted MTB transcription factors (TFs), and assayed global expression following induction of each TF. The MTB DNA binding network consists of ~16,000 binding events from 154 TFs. We identify >50 TF-DNA consensus motifs and >1,150 promoter binding events directly associated with proximal gene regulation. An additional ~4,200 binding events are in promoter windows and represent strong candidates for direct transcriptional regulation under appropriate environmental conditions. However, we also identify >10,000 “dormant” DNA binding events that cannot be linked directly with proximal transcriptional control, suggesting that widespread DNA binding may be a common feature that should be considered when developing global models of coordinated gene expression.

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Section: Resultssupporting

confidence: 88%

The DNA-binding network of Mycobacterium tuberculosi s

et al. 2015

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“…The model TetR from E. coli binds as a dimer to a 15 bp palindrome while QacR from S. aureus binds as a tetramer to a 28 bp palindrome [ 3 ]. A number of TFTRs from M. tuberculosis (Rv3066, KstR, KstR2, BkaR) also bind to palindromic motifs [ 10 , 11 , 13 , 14 ]. Motifs for Mce3R and EthR have also been described but these are larger, more complex, in multiple copies and do not conform to the classical structure of a palindromic sequence separated by a small number of bases [ 15 , 27 ].…”

Section: Resultsmentioning

confidence: 99%

“…The exposure to a series of different conditions inside the host, most of which are hostile, and the presence of actively growing and dormant stages imply a key role for the regulation of gene expression in the success of these pathogens. In M. tuberculosis , TFTRs are involved in controlling the expression of genes required for carbon utilisation, kstR, kstR2 and mce3R [ 10 – 12 ], branched chain amino acid catabolism, bkaR [ 13 ] and antibiotic resistance, Rv3066, ethR [ 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

Global analyses of TetR family transcriptional regulators in mycobacteria indicates conservation across species and diversity in regulated functions

et al. 2015

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BackgroundMycobacteria inhabit diverse niches and display high metabolic versatility. They can colonise both humans and animals and are also able to survive in the environment. In order to succeed, response to environmental cues via transcriptional regulation is required. In this study we focused on the TetR family of transcriptional regulators (TFTRs) in mycobacteria.ResultsWe used InterPro to classify the entire complement of transcriptional regulators in 10 mycobacterial species and these analyses showed that TFTRs are the most abundant family of regulators in all species. We identified those TFTRs that are conserved across all species analysed and those that are unique to the pathogens included in the analysis. We examined genomic contexts of 663 of the conserved TFTRs and observed that the majority of TFTRs are separated by 200 bp or less from divergently oriented genes. Analyses of divergent genes indicated that the TFTRs control diverse biochemical functions not limited to efflux pumps. TFTRs typically bind to palindromic motifs and we identified 11 highly significant novel motifs in the upstream regions of divergently oriented TFTRs. The C-terminal ligand binding domain from the TFTR complement in M. tuberculosis showed great diversity in amino acid sequence but with an overall architecture common to other TFTRs.ConclusionThis study suggests that mycobacteria depend on TFTRs for the transcriptional control of a number of metabolic functions yet the physiological role of the majority of these regulators remain unknown.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-1696-9) contains supplementary material, which is available to authorized users.

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“…LrpG (33), PrpR (34), PccR (35), and PccD (29) participated in propionyl-CoA assimilation. In Mycobacterium, acetyl/propionyl-CoA carboxylase (accD1A1) and branched-chain ␣-keto acid dehydrogenase (bkdABC) exist in the same operon and are regulated by a regulator, BkaR, simultaneously (36). In this study, propionyl-CoA carboxylase genes and the bkd operon were regulated by PccD in S. erythraea.…”

Section: Figmentioning

confidence: 83%

PccD Regulates Branched-Chain Amino Acid Degradation and Exerts a Negative Effect on Erythromycin Production in Saccharopolyspora erythraea

Liu

2018

Appl Environ Microbiol

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Branched-chain amino acid (BCAA) degradation is a major source of propionyl coenzyme A (propionyl-CoA), a key precursor of erythromycin biosynthesis in In this study, we found that the operon, responsible for BCAA degradation, was regulated directly by PccD, a transcriptional regulator of propionyl-CoA carboxylase genes. The transcriptional level of the operon was upregulated 5-fold in a gene deletion strain (Δ strain) and decreased 3-fold in a overexpression strain (WT/pIB-), demonstrating that PccD was a negative transcriptional regulator of the operon. The deletion of significantly improved the Δ strain's growth rate, whereas overexpression repressed WT/pIB- growth rate, in basic Evans medium with 30 mM valine as the sole carbon and nitrogen source. The deletion of and the BcdhE1 gene (genes in the operon) resulted in lower growth rates of Δ and ΔBcdhE1 strains, respectively, on 30 mM valine, further suggesting that the operon is involved in BCAA degradation. Both overexpression (WT/pIB-) and inactivation (Δ strain) improve erythromycin production (38% and 64%, respectively), whereas the erythromycin production of strain WT/pIB- was decreased by 48%. Lastly, we explored the applications of engineering and in an industrial high-erythromycin-producing strain. deletion in industrial strain E3 (E3) improved erythromycin production by 20%, and the overexpression of in E3Δ (E3Δ/pIB-) increased erythromycin production by 39% compared with E3 in an industrial fermentation medium. Addition of 30 mM valine to industrial fermentation medium further improved the erythromycin production by 23%, a 72% increase from the initial strain E3. We describe a operon involved in BCAA degradation in The genes of the operon are repressed by a TetR regulator, PccD. The results demonstrated that PccD controlled the supply of precursors for biosynthesis of erythromycin via regulating the BCAA degradation and propionyl-CoA assimilation and exerted a negative effect on erythromycin production. The findings reveal a regulatory mechanism in feeder pathways and provide new strategies for designing metabolic engineering to increase erythromycin yield.

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bkaRis a TetR-type repressor that controls an operon associated with branched-chain keto-acid metabolism inMycobacteria

Cited by 15 publications

References 27 publications

The DNA-binding network of Mycobacterium tuberculosi s

The DNA-binding network of Mycobacterium tuberculosi s

Global analyses of TetR family transcriptional regulators in mycobacteria indicates conservation across species and diversity in regulated functions

PccD Regulates Branched-Chain Amino Acid Degradation and Exerts a Negative Effect on Erythromycin Production in Saccharopolyspora erythraea

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