Lyngbyatoxin-a: Difference between revisions

| Verifiedfields = changed

| Watchedfields = changed

| verifiedrevid = 451097180

| ImageFile = Lyngbyatoxin A.svg

| SystematicName = (2''S'',5''S'')-9-[(3''R'')-3,7-Dimethylocta-1,6-dien-3-yl]-5-(hydroxymethyl)-1-methyl-2-(propan-2-yl)-1,2,4,5,6,8-hexahydro-3''H''-[1,4]diazonino[7,6,5-''cd'']indol-3-one

| InChI = 1/C27H39N3O2/c1-8-27(6,13-9-10-17(2)3)21-11-12-22-23-19(15-28-24(21)23)14-20(16-31)29-26(32)25(18(4)5)30(22)7/h8,10-12,15,18,20,25,28,31H,1,9,13-14,16H2,2-7H3,(H,29,32)/t20-,25-,27-/m0/s1

| InChIKey = KISDGNGREAJPQR-OICBGKIFBW

| StdInChI_Ref = {{stdinchicite|changed|chemspider}}

| StdInChI = 1S/C27H39N3O2/c1-8-27(6,13-9-10-17(2)3)21-11-12-22-23-19(15-28-24(21)23)14-20(16-31)29-26(32)25(18(4)5)30(22)7/h8,10-12,15,18,20,25,28,31H,1,9,13-14,16H2,2-7H3,(H,29,32)/t20-,25-,27-/m0/s1

| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}

| StdInChIKey = KISDGNGREAJPQR-OICBGKIFSA-N

| CASNo_Ref = {{cascite|correct|??}}

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = SE69L721CS

| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}

| ChemSpiderID = 10472344

| C=27|H=39|N=3|O=2

| MeltingPtC =

| BoilingPtC =

'''Lyngbyatoxin-a''' is a [[cyanotoxin]] produced by certain [[cyanobacteria]] species, most notably ''[[Moorea producens]]'' (formerly ''Lyngbya majuscula''). It is produced as defense mechanism to ward off any would-be predators of the bacterium, being a potent [[blister agent]] as well as [[carcinogen]]. Low concentrations cause a common skin condition known as [[seaweed dermatitis]].<ref>{{cite journal | last1 = Cardellina | first1 = JH | last2 = Marner | first2 = FJ | last3 = Moore | first3 = RE | date = Apr 1979 | title = Seaweed dermatitis: structure of lyngbyatoxin A. | journal = Science | volume = 204 | issue = 4389| pages = 193–5 | pmid = 107586 | doi = 10.1126/science.107586 | bibcode = 1979Sci...204..193C }}</ref><ref>{{cite journal | last1 = Fujiki | first1 = H | last2 = Mori | first2 = M | last3 = Nakayasu | first3 = M | last4 = Terada | first4 = M | last5 = Sugimura | first5 = T | last6 = Moore | first6 = RE | date = Jun 1981 | title = Indole alkaloids: dihydroteleocidin B, teleocidin, and lyngbyatoxin A as members of a new class of tumor promoters | journal = Proceedings of the National Academy of Sciences USA | volume = 78 | issue = 6| pages = 3872–6 | pmid = 6791164 | pmc=319675 | doi=10.1073/pnas.78.6.3872| doi-access = free | bibcode = 1981PNAS...78.3872F }}</ref><ref>{{cite journal | last1 = Kozikowski | first1 = AP | last2 = Shum | first2 = PW | last3 = Basu | first3 = A | last4 = Lazo | first4 = JS | date = Aug 1991 | title = Synthesis of structural analogues of lyngbyatoxin A and their evaluation as activators of protein kinase C. | journal = Journal of Medicinal Chemistry | volume = 34 | issue = 8| pages = 2420–30 | pmid = 1875340 | doi=10.1021/jm00112a017}}</ref><ref>{{cite journal | last1 = Osborne | first1 = NJ | last2 = Webb | first2 = PM | last3 = Shaw | first3 = GR | date = Nov 2001 | title = The toxins of Lyngbya majuscula and their human and ecological health effects | journal = Environment International | volume = 27 | issue = 5| pages = 381–92 | pmid = 11757852 | doi=10.1016/s0160-4120(01)00098-8| bibcode = 2001EnInt..27..381O }}</ref><ref>{{cite journal | last1 = Ito | first1 = E | last2 = Satake | first2 = M | last3 = Yasumoto | first3 = T | date = May 2002 | title = Pathological effects of lyngbyatoxin A upon mice | journal = Toxicon | volume = 40 | issue = 5| pages = 551–6 | pmid = 11821127 | doi=10.1016/s0041-0101(01)00251-3}}</ref><ref>{{cite journal | last1 = Edwards | first1 = DJ | author-link2 = William H. Gerwick | last2 = Gerwick | first2 = WH | year = 2004 | title = Lyngbyatoxin biosynthesis: sequence of biosynthetic gene cluster and identification of a novel aromatic prenyltransferase | journal = Journal of the American Chemical Society | volume = 126 | issue = 37| pages = 11432–3 | pmid = 15366877 | doi = 10.1021/ja047876g }}</ref>

== Biosynthesis ==

[[File:Lyngbyatoxin Biosynthesis2.png|thumb|Lyngbyatoxin Biosynthesis reported by Gerwick et al. and Neilan et al.]]

Lyngbyatoxin is a terpenoid indole alkaloid that belongs to the class of non-ribosomal peptides (NRP).<ref>{{cite journal | doi = 10.1021/cb400189j | volume=8 | title=High-Titer Heterologous Production in E. coli of Lyngbyatoxin, a Protein Kinase C Activator from an Uncultured Marine Cyanobacterium | journal=ACS Chemical Biology | pages=1888–1893| pmc=3880125 | pmid=23751865 | year=2013 | last1 = Ongley | first1 = SE | last2 = Bian | first2 = X | last3 = Zhang | first3 = Y | last4 = Chau | first4 = R | last5 = Gerwick | first5 = WH | last6 = Müller | first6 = R | last7 = Neilan | first7 = BA| issue=9 }}</ref> Lyngbyatoxin contains a nucleophilic indole ring that takes part in the activation of protein kinases. Figure 1, shows the biosynthesis of Lyngbyatoxin reported by Neilan et al. and Gerwick et al. The non-ribosomal peptide synthase (NRPS) LtxA protein condenses L-methyl-valine and L-tryptophan to form the linear dipeptide N-methyl-L-valyl-L-tryptophan. The latter is released via a NADPH-dependent reductive cleavage to form the aldehyde which is subsequently reduced to the corresponding alcohol. Then LtxB which is a P450-dependent monooxygenase serves as a catalyst in the oxidation and subsequent cyclization of N-methyl-L-valyl-L-tryptophan. Finally, LtxC which is a reverse prenyltransferase performs the transfer of a geranyl pyrophosphate (GPP) to carbon-7 of the indole ring which is accompanied by the loss of pyrophosphate.

{{Cyanotoxins}}

[[Category:Indole alkaloids]]

[[Category:Blister agents]]

[[Category:Bacterial alkaloids]]