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Pathway Description
Operon: dcw cluster Genes
Escherichia coli
Category:
Metabolite Pathway
Sub-Category:
Signaling
Created: 2015-09-09
Last Updated: 2019-08-21
The mraZ-rsmH-ftsLI-murEF-mraY-murD-ftsW-murGC-ddlB-ftsQAZ-lpxC operon in E. coli contains a total of 16 genes that are also known as the division cell wall (dcw) gene cluster. These genes are involved in cell division, as well as peptidoglycan synthesis. The only terminator in the operon occurs at the end, so all 16 genes can be transcribed at one time.
The operon can be repressed by the transcriptional regulator protein MraZ, which is encoded by the first gene in the operon. The operon excluding the first two proteins can also be repressed by the LexA repressor protein, which inhibits the promoter upstream of ftsL. LexA binds to the promoter region, preventing RNA polymerase from binding in response to something that would cause DNA replication to be halted. The genes after this promoter do not have additional promoters until the ftsQAZ-lpxC genes, which are further regulated.
Firstly, regulatory protein SdiA can bind to the promoter upstream of ftsQ and repress the transcription of the four downstream genes. The promoter upstream of the ftsA gene can be activated by the transcriptional regulatory protein RcsB, which is involved in regulation of cell division genes and membrane protein synthesis among other functions. Finally, the compound guanosine 3'-diphosphate 5'-triphosphate (ppGpp) can bind to the promoter upstream of the ftsZ gene, activating transcription.
The first gene, mraZ, encodes the transcriptional regulator protein MraZ that regulates the operon.
The second gene, rsmH, encodes ribosomal RNA small subunit methyltransferase H, a protein that methylates 16S rRNA.
The third gene, ftsL, encodes cell division protein FtsL, a protein that is essential for cell division and may link together cytoplasmic and periplasmic cell division proteins.
The fourth gene, ftsI, encodes the peptidoglycan synthase ftsI, another protein essential for cell division that catalyzes cross-linking of the peptidoglycan in the cell wall as the cell divides.
The fifth gene, murE, encodes UDP-N-acetylmuramoyl-L-alanyl-D-glutamate (UMAG) 2,6-diaminopimelate ligase. This protein is an enzyme that adds meso-diaminopimelic acid to UMAG, as part of the biosynthesis of peptidoglycan used in the bacteria's cell wall.
The sixth gene, murF, encodes UDP-N-acetylmuramoyl-tripeptide--D-alanyl-D-alanine ligase. This protein is an enzyme that catalyzes the formation of UDP-N-acetylmuramoyl-pentapeptide, which is a precursor to murein, another name for peptidoglycan.
The seventh gene, mraY, encodes phospho-N-acetylmuramoyl-pentapeptide-transferase. This protein is an enzyme that catalyzes the first step of lipid reactions in peptidoglycan biosynthesis.
The eigth gene, murD, encodes UDP-N-acetylmuramoylalanine--D-glutamate ligase, an enzyme that catalyzes the addition of glutamate to UDP-N-acetylmuramoyl-L-alanine (UMA) as part of peptidoglycan biosynthesis.
The ninth gene, ftsW, encodes a probable peptidoglycan glycosyltransferase protein that functions as a peptidoglycan polymerase. It was previously thought to be a lipid flippase, but there is evidence to suggest that MurJ is instead the flippase.
The tenth gene, murG, encodes UDP-N-acetylglucosamine--N-acetylmuramyl-(pentapeptide) pyrophosphoryl-undecaprenol N-acetylglucosamine transferase. This protein is involved in cell wall formation, catalyzing the formation of undecaprenyl-pyrophosphoryl-MurNAc-(pentapeptide)GlcNAc.
The eleventh gene, MurC, encoes UDP-N-acetylmuramate--L-alanine ligase, a protein that is involved in peptidoglycan biosynthesis and cell wall formation.
The twelfth gene, ddlB, encodes D-alanine--D-alanine ligase B, a protein that catalyzes the addition of two D-alanine molecules together to form D-alanyl-D-alanine, which is involved in peptidoglycan biosynthesis.
The thirteenth gene, ftsQ, encodes cell divison protein FtsQ, an essential cell division protein. It may, along with ftsI, link cytoplasmic and periplasmic cell divions proteins, as well as potentially help formation of the divisome. The divisome is a protein comple that controls cell division.
The fourteenth gene, ftsA, encodes cell division protein FtsA, a protein essential for cell division that helps with the formation and possible anchoring of the Z-ring. The Z-ring is formed from FtsZ protein filaments that form a ring around the centre of the cell and triggers splitting of the cell in two.
The fifteenth gene, ftsZ, encodes cell division protein FtsZ, which is responsible for forming the Z-ring or contractile ring where the cell will divide.
The final gene in the operon, lpxC, encodes UDP-3-O-acyl-N-acetylglucosamine deacetylase. This protein is involved in the biosynthesis of lipid A, a lipid compound found on the outer membrane of gram negative bacteria. Lipid A is considered an endotoxin, and is partially responsible for the activation of an immune response to gram negative bacterial infection.
References
Operon: dcw cluster Genes References
Mohammadi T, Karczmarek A, Crouvoisier M, Bouhss A, Mengin-Lecreulx D, den Blaauwen T: The essential peptidoglycan glycosyltransferase MurG forms a complex with proteins involved in lateral envelope growth as well as with proteins involved in cell division in Escherichia coli. Mol Microbiol. 2007 Aug;65(4):1106-21. doi: 10.1111/j.1365-2958.2007.05851.x. Epub 2007 Jul 19.
Pubmed: 17640276
Vicente M, Gomez MJ, Ayala JA: Regulation of transcription of cell division genes in the Escherichia coli dcw cluster. Cell Mol Life Sci. 1998 Apr;54(4):317-24. doi: 10.1007/s000180050158.
Pubmed: 9614967
Carrion M, Gomez MJ, Merchante-Schubert R, Dongarra S, Ayala JA: mraW, an essential gene at the dcw cluster of Escherichia coli codes for a cytoplasmic protein with methyltransferase activity. Biochimie. 1999 Aug-Sep;81(8-9):879-88.
Pubmed: 10572301
de la Fuente A, Palacios P, Vicente M: Transcription of the Escherichia coli dcw cluster: evidence for distal upstream transcripts being involved in the expression of the downstream ftsZ gene. Biochimie. 2001 Jan;83(1):109-15.
Pubmed: 11254983
Eraso JM, Markillie LM, Mitchell HD, Taylor RC, Orr G, Margolin W: The highly conserved MraZ protein is a transcriptional regulator in Escherichia coli. J Bacteriol. 2014 Jun;196(11):2053-66. doi: 10.1128/JB.01370-13. Epub 2014 Mar 21.
Pubmed: 24659771
Little, J.W., 1991. Mechanism of specific LexA cleavage: autodigestion and the role of RecA coprotease. Biochimie, 73(4), pp.411-421.
Gomez MJ, Fluoret B, van Heijenoort J, Ayala JA: Nucleotide sequence of the regulatory region of the gene pbpB of Escherichia coli. Nucleic Acids Res. 1990 May 11;18(9):2813. doi: 10.1093/nar/18.9.2813.
Pubmed: 2187182
Yura T, Mori H, Nagai H, Nagata T, Ishihama A, Fujita N, Isono K, Mizobuchi K, Nakata A: Systematic sequencing of the Escherichia coli genome: analysis of the 0-2.4 min region. Nucleic Acids Res. 1992 Jul 11;20(13):3305-8. doi: 10.1093/nar/20.13.3305.
Pubmed: 1630901
Blattner FR, Plunkett G 3rd, Bloch CA, Perna NT, Burland V, Riley M, Collado-Vides J, Glasner JD, Rode CK, Mayhew GF, Gregor J, Davis NW, Kirkpatrick HA, Goeden MA, Rose DJ, Mau B, Shao Y: The complete genome sequence of Escherichia coli K-12. Science. 1997 Sep 5;277(5331):1453-62. doi: 10.1126/science.277.5331.1453.
Pubmed: 9278503
Guzman LM, Barondess JJ, Beckwith J: FtsL, an essential cytoplasmic membrane protein involved in cell division in Escherichia coli. J Bacteriol. 1992 Dec;174(23):7716-28.
Pubmed: 1332942
Ueki M, Wachi M, Jung HK, Ishino F, Matsuhashi M: Escherichia coli mraR gene involved in cell growth and division. J Bacteriol. 1992 Dec;174(23):7841-3. doi: 10.1128/jb.174.23.7841-7843.1992.
Pubmed: 1447153
Fujita N, Mori H, Yura T, Ishihama A: Systematic sequencing of the Escherichia coli genome: analysis of the 2.4-4.1 min (110,917-193,643 bp) region. Nucleic Acids Res. 1994 May 11;22(9):1637-9. doi: 10.1093/nar/22.9.1637.
Pubmed: 8202364
Nakamura M, Maruyama IN, Soma M, Kato J, Suzuki H, Horota Y: On the process of cellular division in Escherichia coli: nucleotide sequence of the gene for penicillin-binding protein 3. Mol Gen Genet. 1983;191(1):1-9. doi: 10.1007/bf00330881.
Pubmed: 6350821
Tao JS, Ishiguro EE: Nucleotide sequence of the murE gene of Escherichia coli. Can J Microbiol. 1989 Nov;35(11):1051-4. doi: 10.1139/m89-175.
Pubmed: 2692800
Michaud C, Parquet C, Flouret B, Blanot D, van Heijenoort J: Revised interpretation of the sequence containing the murE gene encoding the UDP-N-acetylmuramyl-tripeptide synthetase of Escherichia coli. Biochem J. 1990 Jul 1;269(1):277-8. doi: 10.1042/bj2690277.
Pubmed: 2198024
Parquet C, Flouret B, Mengin-Lecreulx D, van Heijenoort J: Nucleotide sequence of the murF gene encoding the UDP-MurNAc-pentapeptide synthetase of Escherichia coli. Nucleic Acids Res. 1989 Jul 11;17(13):5379. doi: 10.1093/nar/17.13.5379.
Pubmed: 2668880
Anderson MS, Eveland SS, Onishi HR, Pompliano DL: Kinetic mechanism of the Escherichia coli UDPMurNAc-tripeptide D-alanyl-D-alanine-adding enzyme: use of a glutathione S-transferase fusion. Biochemistry. 1996 Dec 17;35(50):16264-9. doi: 10.1021/bi961872+.
Pubmed: 8973200
Geis A, Plapp R: Phospho-N-acetylmuramoyl-pentapeptide-transferase of Escherichia coli K12. Properties of the membrane-bound and the extracted and partially purified enzyme. Biochim Biophys Acta. 1978 Dec 8;527(2):414-24. doi: 10.1016/0005-2744(78)90355-8.
Pubmed: 215212
Ikeda M, Wachi M, Jung HK, Ishino F, Matsuhashi M: The Escherichia coli mraY gene encoding UDP-N-acetylmuramoyl-pentapeptide: undecaprenyl-phosphate phospho-N-acetylmuramoyl-pentapeptide transferase. J Bacteriol. 1991 Feb;173(3):1021-6. doi: 10.1128/jb.173.3.1021-1026.1991.
Pubmed: 1846850
Ikeda M, Wachi M, Ishino F, Matsuhashi M: Nucleotide sequence involving murD and an open reading frame ORF-Y spacing murF and ftsW in Escherichia coli. Nucleic Acids Res. 1990 Feb 25;18(4):1058. doi: 10.1093/nar/18.4.1058.
Pubmed: 2179861
Mengin-Lecreulx D, van Heijenoort J: Nucleotide sequence of the murD gene encoding the UDP-MurNAc-L-Ala-D-Glu synthetase of Escherichia coli. Nucleic Acids Res. 1990 Jan 11;18(1):183. doi: 10.1093/nar/18.1.183.
Pubmed: 2129548
Boyle DS, Khattar MM, Addinall SG, Lutkenhaus J, Donachie WD: ftsW is an essential cell-division gene in Escherichia coli. Mol Microbiol. 1997 Jun;24(6):1263-73. doi: 10.1046/j.1365-2958.1997.4091773.x.
Pubmed: 9218774
Khattar MM, Begg KJ, Donachie WD: Identification of FtsW and characterization of a new ftsW division mutant of Escherichia coli. J Bacteriol. 1994 Dec;176(23):7140-7. doi: 10.1128/jb.176.23.7140-7147.1994.
Pubmed: 7961485
Khattar MM, Addinall SG, Stedul KH, Boyle DS, Lutkenhaus J, Donachie WD: Two polypeptide products of the Escherichia coli cell division gene ftsW and a possible role for FtsW in FtsZ function. J Bacteriol. 1997 Feb;179(3):784-93. doi: 10.1128/jb.179.3.784-793.1997.
Pubmed: 9006034
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