Lrp of Corynebacterium glutamicum controls expression of the brnFE operon encoding the export system for l-methionine and branched-chain amino acids

Lange, Christian; Mustafi, Nurije; Frunzke, Julia; Kennerknecht, Nicole; Wessel, Mirja; Bott, Michael; Wendisch, Volker F.

doi:10.1016/j.jbiotec.2011.06.003

Cited by 77 publications

(59 citation statements)

References 82 publications

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“…Amino acid-mediated expression control is thought to be another means of avoiding futile cycling, since expression would occur only when the level of the amino acid reaches a certain threshold (14,45). Stimulation of brnFE expression encoding a multi-amino-acid exporter, by methionine and the branched-chain amino acids in conjunction with an Lrp-like transcription factor (45,46) in C. glutamicum and by Lrp and leucine of the inducible LeuE leucine exporter in E. coli (9), is another example, besides those of lysE and argO (described above), where the amino acid substrate exerts control over the expression of its exporter.…”

Section: Discussionmentioning

confidence: 99%

Distinct Paths for Basic Amino Acid Export in Escherichia coli: YbjE (LysO) Mediates Export of l -Lysine

Pathania

Sardesai

2015

J Bacteriol

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In Escherichia coli, argO encodes an exporter for L-arginine (Arg) and its toxic analogue canavanine (CAN), and its transcriptional activation and repression, by Arg and L-lysine (Lys), respectively, are mediated by the regulator ArgP. Accordingly argO and argP mutants are CAN supersensitive (CAN ss IMPORTANCEThis work ascribes a lysine export function to the product of the ybjE gene of Escherichia coli, leading to a physiological scenario wherein two proteins, ArgO and YbjE, perform the task of separately exporting arginine and lysine, respectively, which is distinct from that seen for Corynebacterium glutamicum, where the ortholog of ArgO, LysE, mediates export of both arginine and lysine. Repression of argO transcription by lysine is thought to effect this separation. Accordingly, ArgO mediates lysine export when repression of its transcription by lysine is bypassed. Repression of ybjE transcription by arginine via the ArgR repressor, together with the lysine repression of argO effected by ArgP, is indicative of a mechanism of maintenance of arginine/lysine balance in E. coli. Bacteria possess membrane exporters for a variety of compounds. Their activities to a large extent are thought to play an adaptive role in mitigating the detrimental effects on bacterial growth caused by the presence of biotic stresses, such as those imposed by antibiotics, heavy metals, and other toxic compounds, in their natural environments. While it is easy to come to terms with the existence of proteins that mediate export of compounds described above, the presence of specific export systems for cellular metabolites such as sugars and amino acids appears somewhat enigmatic. For example, Escherichia coli encodes multiple proteins for the export of sugars, such as glucose and lactose (1), and for arabinose (2, 3). In addition, the occurrence of proteins mediating export of amino acids, such as alanine (4), arginine (5), aromatic amino acids (6), cysteine (7, 8), leucine (9), threonine (10, 11) and valine (12), in E. coli has been reported. While the physiological basis for the existence of amino acid exporters is not clear, their occurrence is relatively widespread in bacteria (13,14). It is thought that an amino acid exporter may serve to contribute to the fitness of an organism during conditions of metabolic imbalance resulting from excessive levels of its amino acid substrate in the cytoplasm (13,14). An alternative view could be that export of the amino acid occurs by chance, with the cognate substrate being a naturally occurring structurally related antimetabolite present in the environment. As an example of the latter, one mechanism contributing to the resistance of E. coli to the plant-derived antimetabolite canavanine (CAN), an L-arginine analogue, involves its export by ArgO, the ortholog of the basic amino acid exporter LysE of Corynebacterium glutamicum, following its uptake (5). Harnessing the amino acid export potential of a given bacterium has found widespread application in the commercial production of amin...

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Section: Discussionmentioning

confidence: 99%

Distinct Paths for Basic Amino Acid Export in Escherichia coli: YbjE (LysO) Mediates Export of l -Lysine

Pathania

Sardesai

2015

J Bacteriol

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“…Transcription factor engineering rather lags behind in prokaryotes (see e.g. [197,302,303]), but an example of present interest is the use of marA to improve solvent tolerance (geraniol) in E. coli [304], as this acts, at least in part, by increasing the expression level of the enormous (770kDa) [305] and otherwise somewhat intractable (but see [306]) tolC/acrAB efflux transporter. Mutations in marR [307] and σ 70 (rpoD) [308] can have similar effects.…”

Section: Control Factor Expression Engineeringmentioning

confidence: 99%

Control of metabolite efflux in microbial cell factories: current advances and future prospects

Kell¹

2018

Preprint

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The yield and ease of purification of biotechnological products are typically greatly enhanced if they can be secreted into the external medium. Although not universally appreciated, however, small molecule biotechnological products do not ‘float across’ the phospholipid bilayer portion of biological membranes, and thus they need transporters to assist their passage into the extramembrane and extracellular spaces. Some of these transporters may be reversible, equilibrative transporters that might more normally be used for uptake, while others may have an efflux directionality imposed on them via suitable energy coupling mechanisms. Despite the energetic costs of small molecule synthesis, natural evolution does in fact provide a number of mechanisms by which the secretion of such products can actually enhance fitness. Where available these provide useful starting points, and assaying for such activities is crucial. In particular, in a systems biology approach, we first need to identify such/suitable activities before we can seek to increase them. They may then be improved through promoter engineering, via manipulation of control elements, or by directed evolution of the transporter proteins themselves. Modern methods of synthetic biology provide enormous opportunities for all kinds of efflux transporter engineering; they are just beginning to be realised.

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“…These can, in principle, be optimized by protein engineering and/or evolution. However, in many cases more than one specific effector metabolite influences the activity of a given regulator; in case of Lrp four amino acids (L-methionine and the branched-chain amino acids) have been described (Lange et al, 2011). Thus, the intracellular detection of more than one effector metabolite as well as the typically high rate of false positive clones in FACS screenings clearly necessitates secondary screening, for example, uHPLC, for reliable mutant analysis.…”

Section: Mutant Nomentioning

confidence: 99%

“…The biosensor uses the transcriptional regulator Lrp of C. glutamicum, which activates the expression of the brnFE operon in the presence of increased levels of branched-chain amino acids or L-methionine (Lange et al, 2011). BrnFE, a two-component permease belonging to the LIV-E transporter family, facilitates the export of these amino acids, thus avoiding the inhibitory effects of intracellular amino acid accumulation (Kennerknecht et al, 2002;Trötschel et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

The development and application of a single-cell biosensor for the detection of l-methionine and branched-chain amino acids

Mustafi

Grünberger

Kohlheyer

et al. 2012

Metabolic Engineering

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135

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Lrp of Corynebacterium glutamicum controls expression of the brnFE operon encoding the export system for l-methionine and branched-chain amino acids

Cited by 77 publications

References 82 publications

Distinct Paths for Basic Amino Acid Export in Escherichia coli: YbjE (LysO) Mediates Export of l -Lysine

Distinct Paths for Basic Amino Acid Export in Escherichia coli: YbjE (LysO) Mediates Export of l -Lysine

Control of metabolite efflux in microbial cell factories: current advances and future prospects

The development and application of a single-cell biosensor for the detection of l-methionine and branched-chain amino acids

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