Editing Lysine (section)

=== DAP pathway ===
The DAP pathway is found in both [[prokaryote]]s and plants and begins with the [[dihydrodipicolinate synthase]] (DHDPS) (E.C 4.3.3.7) [[Catalysis|catalysed]] [[condensation reaction]] between the aspartate derived, <small>L</small>-aspartate semialdehyde, and [[Pyruvic acid|pyruvate]] to form (4''S'')-4-hydroxy-2,3,4,5-tetrahydro-(2''S'')-dipicolinic acid (HTPA).<ref name="Atkinson_2013">{{cite journal | vauthors = Atkinson SC, Dogovski C, Downton MT, Czabotar PE, Dobson RC, Gerrard JA, Wagner J, Perugini MA | title = Structural, kinetic and computational investigation of Vitis vinifera DHDPS reveals new insight into the mechanism of lysine-mediated allosteric inhibition | journal = Plant Molecular Biology | volume = 81 | issue = 4–5 | pages = 431–446 | date = March 2013 | pmid = 23354837 | doi = 10.1007/s11103-013-0014-7 | hdl = 11343/282680 | s2cid = 17129774 | hdl-access = free }}</ref><ref name="Griffin_2012">{{cite journal | vauthors = Griffin MD, Billakanti JM, Wason A, Keller S, Mertens HD, Atkinson SC, Dobson RC, Perugini MA, Gerrard JA, Pearce FG | title = Characterisation of the first enzymes committed to lysine biosynthesis in Arabidopsis thaliana | journal = PLOS ONE | volume = 7 | issue = 7 | pages = e40318 | date = 2012 | pmid = 22792278 | pmc = 3390394 | doi = 10.1371/journal.pone.0040318 | bibcode = 2012PLoSO...740318G | doi-access = free }}</ref><ref name="Soares_da_Costa_2010">{{cite journal | vauthors = Soares da Costa TP, Muscroft-Taylor AC, Dobson RC, Devenish SR, Jameson GB, Gerrard JA | title = How essential is the 'essential' active-site lysine in dihydrodipicolinate synthase? | journal = Biochimie | volume = 92 | issue = 7 | pages = 837–845 | date = July 2010 | pmid = 20353808 | doi = 10.1016/j.biochi.2010.03.004 }}</ref><ref name="Soares_da_Costa_2015">{{cite book | vauthors = Soares da Costa TP, Christensen JB, Desbois S, Gordon SE, Gupta R, Hogan CJ, Nelson TG, Downton MT, Gardhi CK, Abbott BM, Wagner J, Panjikar S, Perugini MA | chapter = Quaternary Structure Analyses of an Essential Oligomeric Enzyme | volume = 562 | pages = 205–223 | date = 2015 | pmid = 26412653 | doi = 10.1016/bs.mie.2015.06.020 | series = Methods in Enzymology | isbn = 9780128029084 | title = Analytical Ultracentrifugation }}</ref><ref>{{cite journal | vauthors = Muscroft-Taylor AC, Soares da Costa TP, Gerrard JA | title = New insights into the mechanism of dihydrodipicolinate synthase using isothermal titration calorimetry | journal = Biochimie | volume = 92 | issue = 3 | pages = 254–262 | date = March 2010 | pmid = 20025926 | doi = 10.1016/j.biochi.2009.12.004 }}</ref> The product is then [[Redox|reduced]] by [[4-hydroxy-tetrahydrodipicolinate reductase|dihydrodipicolinate reductase (DHDPR)]] (E.C 1.3.1.26), with [[Nicotinamide adenine dinucleotide phosphate|NAD(P)H]] as a proton donor, to yield 2,3,4,5-tetrahydrodipicolinate (THDP).<ref>{{cite journal | vauthors = Christensen JB, Soares da Costa TP, Faou P, Pearce FG, Panjikar S, Perugini MA | title = Structure and Function of Cyanobacterial DHDPS and DHDPR | journal = Scientific Reports | volume = 6 | issue = 1 | pages = 37111 | date = November 2016 | pmid = 27845445 | pmc = 5109050 | doi = 10.1038/srep37111 | bibcode = 2016NatSR...637111C }}</ref> From this point on, four pathway variations have been found, namely the acetylase, aminotransferase, dehydrogenase, and succinylase pathways.<ref name="Hudson_2005" /><ref>{{cite journal | vauthors = McCoy AJ, Adams NE, Hudson AO, Gilvarg C, Leustek T, Maurelli AT | title = <small>L</small>,<small>L</small>-diaminopimelate aminotransferase, a trans-kingdom enzyme shared by Chlamydia and plants for synthesis of diaminopimelate/lysine | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 103 | issue = 47 | pages = 17909–17914 | date = November 2006 | pmid = 17093042 | pmc = 1693846 | doi = 10.1073/pnas.0608643103 | bibcode = 2006PNAS..10317909M | doi-access = free }}</ref> Both the acetylase and succinylase variant pathways use four [[enzyme]] catalysed steps, the aminotransferase pathway uses two enzymes, and the dehydrogenase pathway uses a single enzyme.<ref>{{cite journal | vauthors = Hudson AO, Gilvarg C, Leustek T | title = Biochemical and phylogenetic characterization of a novel diaminopimelate biosynthesis pathway in prokaryotes identifies a diverged form of <small>LL</small>-diaminopimelate aminotransferase | journal = Journal of Bacteriology | volume = 190 | issue = 9 | pages = 3256–3263 | date = May 2008 | pmid = 18310350 | pmc = 2347407 | doi = 10.1128/jb.01381-07 }}</ref> These four variant pathways converge at the formation of the penultimate product,  ''meso''‑diaminopimelate, which is subsequently enzymatically [[Decarboxylation|decarboxylated]] in an irreversible reaction catalysed by [[Diaminopimelate decarboxylase|diaminopimelate decarboxylase (DAPDC)]] (E.C 4.1.1.20) to produce <small>L</small>-lysine.<ref>{{cite journal | vauthors = Peverelli MG, Perugini MA | title = An optimized coupled assay for quantifying diaminopimelate decarboxylase activity | journal = Biochimie | volume = 115 | pages = 78–85 | date = August 2015 | pmid = 25986217 | doi = 10.1016/j.biochi.2015.05.004 }}</ref><ref name="Soares_da_Costa_2016">{{cite journal | vauthors = Soares da Costa TP, Desbois S, Dogovski C, Gorman MA, Ketaren NE, Paxman JJ, Siddiqui T, Zammit LM, Abbott BM, Robins-Browne RM, Parker MW, Jameson GB, Hall NE, Panjikar S, Perugini MA | title = Structural Determinants Defining the Allosteric Inhibition of an Essential Antibiotic Target | journal = Structure | volume = 24 | issue = 8 | pages = 1282–1291 | date = August 2016 | pmid = 27427481 | doi = 10.1016/j.str.2016.05.019 | doi-access = free }}</ref> The DAP pathway is regulated at multiple levels, including upstream at the enzymes involved in aspartate processing as well as at the initial DHDPS catalysed condensation step.<ref name="Soares_da_Costa_2016" /><ref name="Jander_2009">{{cite journal | vauthors = Jander G, Joshi V | title = Aspartate-Derived Amino Acid Biosynthesis in Arabidopsis thaliana | journal = The Arabidopsis Book | volume = 7 | pages = e0121 | date = 2009-01-01 | pmid = 22303247 | pmc = 3243338 | doi = 10.1199/tab.0121 }}</ref> Lysine imparts a strong [[negative feedback]] loop on these enzymes and, subsequently, regulates the entire pathway.<ref name="Jander_2009" />