Abstract
Pyridoxal 5’-phosphate (PLP) is an essential cofactor for nearly 60 Escherichia coli enzymes but is a highly reactive molecule that is toxic in its free form. How PLP levels are regulated and how PLP is delivered to target enzymes are still open questions. The COG0325 protein family belongs to the fold-type III class of PLP enzymes and binds PLP but has no known biochemical activity although it occurs in all kingdoms of life. Various pleiotropic phenotypes of the E. coli COG0325 (yggS) mutant have been reported, some of which were reproduced and extended in this study. Comparative genomic, genetic and metabolic analyses suggest that these phenotypes reflect an imbalance in PLP homeostasis. The E. coli yggS mutant accumulates the PLP precursor pyridoxine 5’-phosphate (PNP) and is sensitive to an excess of pyridoxine but not of pyridoxal. The pyridoxine toxicity phenotype is complemented by the expression of eukaryotic yggS orthologs. It is also suppressed by the presence of amino acids, specifically isoleucine, threonine and leucine, suggesting the PLP-dependent enzyme transaminase B (IlvE) is affected. These genetic results lay a foundation for future biochemical studies of the role of COG0325 proteins in PLP homeostasis.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 694-706 |
| Number of pages | 13 |
| Journal | Microbiology (United Kingdom) |
| Volume | 162 |
| Issue number | 4 |
| DOIs | |
| State | Published - Apr 1 2016 |
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ASJC Scopus subject areas
- Microbiology
Cite this
Evidence that COG0325 proteins are involved in PLP homeostasis. / Prunetti, Laurence; El Yacoubi, Basma; Schiavon, Cara R.; Kirkpatrick, Ericka; Huang, Lili; Bailly, Marc; El Badawi-Sidhu, Mona; Harrison, Katherine; Gregory, Jesse F.; Fiehn, Oliver; Hanson, Andrew D.; De Crécy-Lagard, Valérie.
In: Microbiology (United Kingdom), Vol. 162, No. 4, 01.04.2016, p. 694-706.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Evidence that COG0325 proteins are involved in PLP homeostasis
AU - Prunetti, Laurence
AU - El Yacoubi, Basma
AU - Schiavon, Cara R.
AU - Kirkpatrick, Ericka
AU - Huang, Lili
AU - Bailly, Marc
AU - El Badawi-Sidhu, Mona
AU - Harrison, Katherine
AU - Gregory, Jesse F.
AU - Fiehn, Oliver
AU - Hanson, Andrew D.
AU - De Crécy-Lagard, Valérie
PY - 2016/4/1
Y1 - 2016/4/1
N2 - Pyridoxal 5’-phosphate (PLP) is an essential cofactor for nearly 60 Escherichia coli enzymes but is a highly reactive molecule that is toxic in its free form. How PLP levels are regulated and how PLP is delivered to target enzymes are still open questions. The COG0325 protein family belongs to the fold-type III class of PLP enzymes and binds PLP but has no known biochemical activity although it occurs in all kingdoms of life. Various pleiotropic phenotypes of the E. coli COG0325 (yggS) mutant have been reported, some of which were reproduced and extended in this study. Comparative genomic, genetic and metabolic analyses suggest that these phenotypes reflect an imbalance in PLP homeostasis. The E. coli yggS mutant accumulates the PLP precursor pyridoxine 5’-phosphate (PNP) and is sensitive to an excess of pyridoxine but not of pyridoxal. The pyridoxine toxicity phenotype is complemented by the expression of eukaryotic yggS orthologs. It is also suppressed by the presence of amino acids, specifically isoleucine, threonine and leucine, suggesting the PLP-dependent enzyme transaminase B (IlvE) is affected. These genetic results lay a foundation for future biochemical studies of the role of COG0325 proteins in PLP homeostasis.
AB - Pyridoxal 5’-phosphate (PLP) is an essential cofactor for nearly 60 Escherichia coli enzymes but is a highly reactive molecule that is toxic in its free form. How PLP levels are regulated and how PLP is delivered to target enzymes are still open questions. The COG0325 protein family belongs to the fold-type III class of PLP enzymes and binds PLP but has no known biochemical activity although it occurs in all kingdoms of life. Various pleiotropic phenotypes of the E. coli COG0325 (yggS) mutant have been reported, some of which were reproduced and extended in this study. Comparative genomic, genetic and metabolic analyses suggest that these phenotypes reflect an imbalance in PLP homeostasis. The E. coli yggS mutant accumulates the PLP precursor pyridoxine 5’-phosphate (PNP) and is sensitive to an excess of pyridoxine but not of pyridoxal. The pyridoxine toxicity phenotype is complemented by the expression of eukaryotic yggS orthologs. It is also suppressed by the presence of amino acids, specifically isoleucine, threonine and leucine, suggesting the PLP-dependent enzyme transaminase B (IlvE) is affected. These genetic results lay a foundation for future biochemical studies of the role of COG0325 proteins in PLP homeostasis.
UR - http://www.scopus.com/inward/record.url?scp=84963858093&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84963858093&partnerID=8YFLogxK
U2 - 10.1099/mic.0.000255
DO - 10.1099/mic.0.000255
M3 - Article
AN - SCOPUS:84963858093
VL - 162
SP - 694
EP - 706
JO - Microbiology (United Kingdom)
JF - Microbiology (United Kingdom)
SN - 1350-0872
IS - 4
ER -