Editing Peptidoglycan (section)

== Biosynthesis ==
The peptidoglycan monomers are synthesized in the [[cytosol]] and are then attached to a membrane carrier [[bactoprenol]].  Bactoprenol transports peptidoglycan monomers across the cell membrane where they are inserted into the existing peptidoglycan.<ref name="The Prokaryotic Cell">{{cite web |url=http://student.ccbcmd.edu/courses/bio141/lecguide/unit1/prostruct/cw.html |title= The Prokaryotic Cell: Bacteria |access-date=1 May 2011 |archive-url= https://web.archive.org/web/20100726231059/http://student.ccbcmd.edu/courses/bio141/lecguide/unit1/prostruct/cw.html |archive-date=26 July 2010 }}</ref>

# In the first step of peptidoglycan synthesis, [[glutamine]], which is an amino acid, donates an amino group to a sugar, [[fructose 6-phosphate]].<ref name="White-2007"/> This reaction, catalyzed by [[EC 2.6.1.16]] (GlmS), turns fructose 6-phosphate into [[glucosamine-6-phosphate]].<ref name="Otten-2018">{{cite journal | vauthors = Otten C, Brilli M, Vollmer W, Viollier PH, Salje J | title = Peptidoglycan in obligate intracellular bacteria | journal = Molecular Microbiology | volume = 107 | issue = 2 | pages = 142–163 | date = January 2018 | pmid = 29178391 | doi = 10.1111/mmi.13880 | pmc = 5814848 | doi-access = free }}</ref>
# In step two, an acetyl group is transferred from [[acetyl CoA]] to the amino group on the glucosamine-6-phosphate creating [[N-acetyl-glucosamine-6-phosphate|''N''-acetyl-glucosamine-6-phosphate]].<ref name="White-2007"/> This reaction is [[EC 5.4.2.10]], catalyzed by GlmM.<ref name="Otten-2018"/>
# {{anchor|GlmU}}In step three of the synthesis process, the ''N''-acetyl-glucosamine-6-phosphate is isomerized, which will change ''N''-acetyl-glucosamine-6-phosphate to [[N-acetyl-glucosamine-1-phosphate|''N''-acetyl-glucosamine-1-phosphate]].<ref name="White-2007"/> This is [[EC 2.3.1.157]], catalyzed by GlmU.<ref name="Otten-2018"/>
# In step 4, the ''N''-acetyl-glucosamine-1-phosphate, which is now a monophosphate, attacks [[Uridine triphosphate|UTP]].  Uridine triphosphate, which is a [[pyrimidine]] [[nucleotide]], has the ability to act as an energy source. In this particular reaction, after the monophosphate has attacked the UTP, an inorganic pyrophosphate is given off and is replaced by the monophosphate, creating UDP-N-acetylglucosamine (2,4). (When [[Uridine diphosphate|UDP]] is used as an energy source, it gives off an inorganic phosphate.) This initial stage, is used to create the precursor for the NAG in peptidoglycan.<ref name="White-2007"/> This is [[EC 2.7.7.23]], also catalyzed by GlmU, which is a bifunctional enzyme.<ref name="Otten-2018"/>
# In step 5, some of the UDP-N-acetylglucosamine (UDP-GlcNAc) is converted to UDP-MurNAc (UDP-N-acetylmuramic acid) by the addition of a lactyl group to the glucosamine. Also in this reaction, the C3 hydroxyl group will remove a phosphate from the alpha carbon of [[Phosphoenolpyruvic acid|phosphoenolpyruvate]]. This creates what is called an enol derivative.<ref name="White-2007"/> [[EC 2.5.1.7]], catalyzed by MurA.<ref name="Otten-2018"/>
# In step 6, the enol is reduced to a "lactyl moiety" by NADPH in step six.<ref name="White-2007"/> [[EC 1.3.1.98]], catalyzed by MurB.<ref name="Otten-2018"/>
# In step 7, the UDP–MurNAc is converted to UDP-MurNAc pentapeptide by the addition of five amino acids, usually including the dipeptide <small>D</small>-alanyl-<small>D</small>-alanine.<ref name="White-2007"/> This is a string of three reactions: [[EC 6.3.2.8]] by MurC, [[EC 6.3.2.9]] by MurD, and [[EC 6.3.2.13]] by MurE.<ref name="Otten-2018"/>

Each of these reactions requires the energy source ATP.<ref name="White-2007"/>  This is all referred to as Stage one.

Stage two occurs in the cytoplasmic membrane. It is in the membrane where a lipid carrier called [[bactoprenol]] carries peptidoglycan precursors through the cell membrane.
# [[Undecaprenyl phosphate]] will attack the UDP-MurNAc penta, creating a PP-MurNac penta, which is now a lipid ([[lipid I]]).<ref name="White-2007"/> [[EC 2.7.8.13]] by MraY.<ref name="Otten-2018"/>
# UDP-GlcNAc is then transported to MurNAc, creating Lipid-PP-MurNAc penta-GlcNAc ([[lipid II]]), a disaccharide, also a precursor to peptidoglycan.<ref name="White-2007"/> [[EC 2.4.1.227]] by MurG.<ref name="Otten-2018"/>
# Lipid II is transported across the membrane by [[flippase]] (MurJ), a discovery made in 2014 after decades of searching.<ref name="Sham-2014">{{cite journal | vauthors = Sham LT, Butler EK, Lebar MD, Kahne D, Bernhardt TG, Ruiz N | title = Bacterial cell wall. MurJ is the flippase of lipid-linked precursors for peptidoglycan biogenesis | journal = Science | volume = 345 | issue = 6193 | pages = 220–222 | date = July 2014 | pmid = 25013077 | pmc = 4163187 | doi = 10.1126/science.1254522 | bibcode = 2014Sci...345..220S }}</ref> Once it is there, it is added to the growing glycan chain by the enzyme [[peptidoglycan glycosyltransferase]] (GTase, EC 2.4.1.129). This reaction is known as transglycosylation.  In the reaction, the hydroxyl group of the GlcNAc will attach to the MurNAc in the glycan, which will displace the lipid-PP from the glycan chain.<ref name="White-2007">{{cite book | vauthors = White D |year=2007 |title=The physiology and biochemistry of prokaryotes |edition=3rd |location=NY |publisher=Oxford University Press Inc.}}</ref>
# In a final step, the [[DD-Transpeptidase|<small>DD</small>-transpeptidase]] (TPase, EC 3.4.16.4) crosslinks individual glycan chains. This protein is also known as the [[penicillin-binding protein]]. Some versions of the enzyme also performs the glycosyltransferase function, while others leave the job to a separate enzyme.<ref name="Otten-2018"/>
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