pyrrolnitrin
{{chembox
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 444574505
| ImageFile = Pyrrolnitrin.svg
| ImageSize = 150px
| PIN = 3-Chloro-4-(3-chloro-2-nitrophenyl)-1H-pyrrole
| OtherNames =
|Section1={{Chembox Identifiers
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = N0P24B6EDQ
| CASNo_Ref = {{cascite|correct|??}}
| CASNo = 1018-71-9
| PubChem = 13916
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D01094
| ChEBI_Ref = {{ebicite|changed|EBI}}
| ChEBI = 32079
| SMILES = C1=CC(=C(C(=C1)Cl)[N+](=O)[O-])C2=CNC=C2Cl
| EINECS = 213-812-7
| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
| ChemSpiderID = 13314
| InChI = 1/C10H6Cl2N2O2/c11-8-3-1-2-6(10(8)14(15)16)7-4-13-5-9(7)12/h1-5,13H
| InChIKey = QJBZDBLBQWFTPZ-UHFFFAOYAG
| StdInChI_Ref = {{stdinchicite|changed|chemspider}}
| StdInChI = 1S/C10H6Cl2N2O2/c11-8-3-1-2-6(10(8)14(15)16)7-4-13-5-9(7)12/h1-5,13H
| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}
| StdInChIKey = QJBZDBLBQWFTPZ-UHFFFAOYSA-N
| RTECS =
| MeSHName = D011764
}}
|Section2={{Chembox Properties
| Formula=C10H6Cl2N2O2
| MolarMass=257.07284
| Appearance=
| Density=
| MeltingPt=
| BoilingPt=
| Solubility=
}}
|Section6={{Chembox Pharmacology
| ATCCode_prefix = D01
| ATCCode_suffix = AA07
}}
|Section7={{Chembox Hazards
| MainHazards=
| FlashPt=
| AutoignitionPt =
}}
}}
Pyrrolnitrin (PRN{{Cite journal |last1=Kirner |first1=Sabine |last2=Hammer |first2=Philip E. |last3=Hill |first3=D. Steven |last4=Altmann |first4=Annett |last5=Fischer |first5=Ilona |last6=Weislo |first6=Laura J. |last7=Lanahan |first7=Mike |last8=van Pée |first8=Karl-Heinz |last9=Ligon |first9=James M. |date=April 1998 |title=Functions Encoded by Pyrrolnitrin Biosynthetic Genes from Pseudomonas fluorescens |journal=Journal of Bacteriology |language=en |volume=180 |issue=7 |pages=1939–1943 |doi=10.1128/JB.180.7.1939-1943.1998 |issn=0021-9193 |pmc=107110 |pmid=9537395}}) is a naturally occurring phenylpyrrole fungicide.{{Cite journal
| last1 = Gordee | first1 = R. S.
| last2 = Matthews | first2 = T. R.
| title = Systemic antifungal activity of pyrrolnitrin
| journal = Applied Microbiology
| volume = 17
| issue = 5
| pages = 690–694
| year = 1969
| doi = 10.1128/AEM.17.5.690-694.1969
| pmid = 5785951
| pmc = 377781
}} Pseudomonas and Burkholderia species produce pyrrolnitrin from tryptophan as secondary metabolite.{{Cite journal
| last1 = Zhu | first1 = X.
| last2 = Van Pee | first2 = K. -H.
| last3 = Naismith | first3 = J. H.
| doi = 10.1074/jbc.M110.120485
| title = The Ternary Complex of PrnB (the Second Enzyme in the Pyrrolnitrin Biosynthesis Pathway), Tryptophan, and Cyanide Yields New Mechanistic Insights into the Indolamine Dioxygenase Superfamily
| journal = Journal of Biological Chemistry
| volume = 285
| issue = 27
| pages = 21126–21133
| year = 2010
| pmid = 20421301
| pmc =2898318
| doi-access = free
| last1 = Park | first1 = J. Y.
| last2 = Oh | first2 = S. A.
| last3 = Anderson | first3 = A. J.
| last4 = Neiswender | first4 = J.
| last5 = Kim | first5 = J. -C.
| last6 = Kim | first6 = Y. C.
| doi = 10.1111/j.1472-765X.2011.03036.x
| title = Production of the antifungal compounds phenazine and pyrrolnitrin from Pseudomonas chlororaphis O6 is differentially regulated by glucose
| journal = Letters in Applied Microbiology
| volume = 52
| issue = 5
| pages = 532–537
| year = 2011
| pmid = 21362001
| pmc =
| doi-access = free
}} It is believed that the antifungal properties come from inhibition of electron transport system.{{Cite journal |last1=De Laurentis |first1=Walter |last2=Khim |first2=Leang |last3=Anderson |first3=J. L. Ross |last4=Adam |first4=Ariane |last5=Phillips |first5=Robert S. |last6=Chapman |first6=Stephen K. |last7=van Pee |first7=Karl-Heinz |last8=Naismith |first8=James H. |date=2007-10-01 |title=The Second Enzyme in Pyrrolnitrin Biosynthetic Pathway Is Related to the Heme-Dependent Dioxygenase Superfamily |journal=Biochemistry |language=en |volume=46 |issue=43 |pages=12393–12404 |doi=10.1021/bi7012189 |issn=0006-2960 |pmc=3326534 |pmid=17924666}}
The synthetic fungicides fenpiclonil and fludioxonil are chemically related to pyrrolnitrin.{{cite book|last1=Pillonel|first1=Ch|title=Encyclopedia of Agrochemicals|last2=Knauf-beiter|first2=G.|last3=Steinemann|first3=A.|year=2003|doi=10.1002/047126363X.agr106|chapter=Fungicides, Phenylpyrroles|isbn=047126363X}}{{cite journal|last1=Jespers|first1=A.B.K.|last2=Davidse|first2=L.C.|last3=Dewaard|first3=M.A.|title=Biochemical Effects of the Phenylpyrrole Fungicide Fenpiclonil in Fusarium sulphureum (Schlecht)|journal=Pesticide Biochemistry and Physiology|volume=45|issue=2|year=1993|pages=116–129|issn=0048-3575|doi=10.1006/pest.1993.1014}}
Biosynthesis
In Pseudomonas fluorescens, biosynthesis of pyrrolnitrin requires four genes, named prnABCD, arranged into a single operon. The products of these genes are similar in size and catalyze four subsequent reactions:
- prnA – chlorination of L-tryptophan to 7-chloro-L-tryptophan (7-CLT), in a process requiring NAD
- prnB – ring rearrangement and decarboxylation of 7-chloro-L-tryptophan to form monodechloroaminopyrrolnitrin (MAD)
- prnC – chlorination of monodechloroaminopyrrolnitrin to form aminopyrrolnitrin (APRN), in a process also requiring NAD
- prnD – oxidation of the amino group of APRN to a nitro group thus completing the biosynthesis of pyrrolnitrin.
File:Pyrrolnitrin_biosynthesis.tif
Except for prnA, these enzymes are unable to act on D-tryptophan.
Neither of the chlorinating enzymes, prnA nor prnC, show homology to known haloperoxidases nor to one another.
An alternative pathway was also suggested, where L-tryptophan is first turned into aminophenylpyrrole (APP) and then by subsequent steps to aminopyrrolnitrin and pyrrolnitrin. While these steps have not been described in more detail, prnB is able to produce APP, presumably from tryptophan as starting material. APP seems to be an unwanted side product. The gene coding for prnB also starts with the unusual GTG start codon, further lowering the amount of prnB expressed and thus lowering the amount of present APP.