Nucleotide metabolism and its control in lactic acid bacteria

Kilstrup, Mogens; Hammer, Karin; Jensen, Peter Ruhdal; Martinussen, Jan

doi:10.1016/j.fmrre.2005.04.006

Cited by 236 publications

(208 citation statements)

References 154 publications

(236 reference statements)

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“…Besides the known purine-regulated promoters, on which PurR regulation has been experimentally verified, several other promoters have been found to possess PurBox motifs (Beyer et al, 2003;Guédon et al, 2002;Kilstrup et al, 2005). A number of these putative purine-regulated promoters are located upstream of genes involved in purine biosynthesis.…”

Section: Introductionmentioning

confidence: 99%

The PurR regulon in Lactococcus lactis – transcriptional regulation of the purine nucleotide metabolism and translational machinery

2012

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Purine nucleotides are either synthesized de novo from 5-phosphoribosyl-1-pyrophosphate (PRPP) or salvaged from the environment. In Lactococcus lactis, transcription of the de novo synthesis operons, purCSQLF and purDEK, has genetically been shown to be activated by the PurR protein when bound to a conserved PurBox motif present on the DNA at a fixed distance from the promoter "10 element. PurR contains a PRPP-binding site, and activation occurs when the intracellular PRPP pool is high as a consequence of low exogenous purine nucleotide pools. By an iterative approach of bioinformatics searches and motif optimization, 21 PurR-regulated genes were identified and used in a redefinition of the PurBox consensus sequence. In the process a new motif, the double-PurBox, which is present in a number of promoters and contains two partly overlapping PurBox motifs, was established. Transcriptional fusions were used to analyse wild-type promoters and promoters with inactivating PurBox mutations to confirm the relevance of the PurBox motifs as PurR-binding sites. The promoters of several operons were shown to be devoid of any "35 sequence, and found to be completely dependent on PurRmediated activation. This suggests that binding of the PurR protein to the PurBox takes over the role of the "35 sequence. The study has expanded the PurR regulon to include promoters in nucleotide metabolism, C 1 compound metabolism, phosphonate transport, pyrophosphatase activity, (p)ppGpp metabolism, and translation-related functions. Of special interest is the presence of PurBox motifs in rrn promoters, suggesting a novel connection between nucleotide availability and the translational machinery.

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Section: Introductionmentioning

confidence: 99%

The PurR regulon in Lactococcus lactis – transcriptional regulation of the purine nucleotide metabolism and translational machinery

2012

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“…The facilitated production of riboflavin is also indicated by an increase in L-glutamine utilization (Fig. S2), since the latter amino acid is involved in the biosynthesis of nucleotides (Kilstrup et al, 2005).…”

Section: Discussionmentioning

confidence: 89%

Excess of threonine compared with serine promotes threonine aldolase activity in Lactococcus lactis IL1403

et al. 2015

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“…cbs_1975 encodes an adenine deaminase, responsible for converting adenosine to inosine in the nucleotide salvage pathway (Kilstrup et al, 2005). In SA-1, a SNV at position 1707 position in the coding sequence of a GAT produced an amino acid change from alanine to serine at position 11 (A11S).…”

Section: Snvsmentioning

confidence: 99%

Comparative phenotypic analysis and genome sequence of Clostridium beijerinckii SA-1, an offspring of NCIMB 8052

et al. 2013

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Production of butanol by solventogenic clostridia is controlled through metabolic regulation of the carbon flow and limited by its toxic effects. To overcome cell sensitivity to solvents, stressdirected evolution methodology was used three decades ago on Clostridium beijerinckii NCIMB 8052 that spawned the SA-1 strain. Here, we evaluated SA-1 solventogenic capabilities when growing on a previously validated medium containing, as carbon-and energy-limiting substrates, sucrose and the products of its hydrolysis D-glucose and D-fructose and only D-fructose. Comparative small-scale batch fermentations with controlled pH (pH 6.5) showed that SA-1 is a solvent hyper-producing strain capable of generating up to 16.1 g l "1 of butanol and 26.3 g l "1 of total solvents, 62.3 % and 63 % more than NCIMB 8052, respectively. This corresponds to butanol and solvent yields of 0.3 and 0.49 g g "1 , respectively (63 % and 65 % increase compared with NCIMB 8052). SA-1 showed a deficiency in D-fructose transport as suggested by its 7 h generation time compared with 1 h for NCIMB 8052. To potentially correlate physiological behaviour with genetic mutations, the whole genome of SA-1 was sequenced using the Illumina GA IIx platform. PCR and Sanger sequencing were performed to analyse the putative variations. As a result, four errors were confirmed and validated in the reference genome of NCIMB 8052 and a total of 10 genetic polymorphisms in SA-1. The genetic polymorphisms included eight single nucleotide variants, one small deletion and one large insertion that it is an additional copy of the insertion sequence ISCb1. Two of the genetic polymorphisms, the serine threonine phosphatase cbs_4400 and the solute binding protein cbs_0769, may possibly explain some of the observed physiological behaviour, such as rerouting of the metabolic carbon flow, deregulation of the D-fructose phosphotransferase transport system and delayed sporulation.

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Nucleotide metabolism and its control in lactic acid bacteria

Cited by 236 publications

References 154 publications

The PurR regulon in Lactococcus lactis – transcriptional regulation of the purine nucleotide metabolism and translational machinery

The PurR regulon in Lactococcus lactis – transcriptional regulation of the purine nucleotide metabolism and translational machinery

Excess of threonine compared with serine promotes threonine aldolase activity in Lactococcus lactis IL1403

Comparative phenotypic analysis and genome sequence of Clostridium beijerinckii SA-1, an offspring of NCIMB 8052

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