Pyrrolnitrin Explained

Pyrrolnitrin (PRN^[1]) is a phenylpyrrole chemical used an antifungal antibiotic.^[2] Pseudomonas pyrrocinia and other Pseudomonas species produce pyrrolnitrin from tryptophan as secondary metabolite.^{[3] [4]} It is believed that the antifungal properties come from inhibition of electron transport system.^[5]

The synthetic fungicides fenpiclonil and fludioxonil are chemically related to pyrrolnitrin.^{[6] [7]}

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), requiring NAD for its activity
• prnB – ring rearrangement and decarboxylation of 7-chloro-L-tryptophan to form monodechloroaminopyrrolnitrin (MAD)
• prnC – chlorination of monodechloroaminopyrrolnitrin to form aminopyrrolnitrin (APRN), requiring NAD for its activity
• prnD – oxidation of amino group to form nitro group of pyrrolnitrin

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.

Notes and References

1. Kirner . Sabine . Hammer . Philip E. . Hill . D. Steven . Altmann . Annett . Fischer . Ilona . Weislo . Laura J. . Lanahan . Mike . van Pée . Karl-Heinz . Ligon . James M. . April 1998 . Functions Encoded by Pyrrolnitrin Biosynthetic Genes from Pseudomonas fluorescens . Journal of Bacteriology . en . 180 . 7 . 1939–1943 . 10.1128/JB.180.7.1939-1943.1998 . 0021-9193 . 107110 . 9537395.
2. Gordee . R. S.. Matthews . T. R.. Systemic antifungal activity of pyrrolnitrin. Applied Microbiology. 17. 5. 690–694. 1969. 10.1128/AEM.17.5.690-694.1969. 5785951. 377781.
3. Zhu . X.. Van Pee . K. -H.. Naismith . J. H.. 10.1074/jbc.M110.120485. 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 of Biological Chemistry. 285. 27. 21126–21133. 2010. 20421301. 2898318. free.
4. Park . J. Y.. Oh . S. A.. Anderson . A. J.. Neiswender . J.. Kim . J. -C.. Kim . Y. C.. 10.1111/j.1472-765X.2011.03036.x. Production of the antifungal compounds phenazine and pyrrolnitrin from Pseudomonas chlororaphis O6 is differentially regulated by glucose. Letters in Applied Microbiology. 52. 5. 532–537. 2011. 21362001. free.
5. De Laurentis . Walter . Khim . Leang . Anderson . J. L. Ross . Adam . Ariane . Phillips . Robert S. . Chapman . Stephen K. . van Pee . Karl-Heinz . Naismith . James H. . 2007-10-01 . The Second Enzyme in Pyrrolnitrin Biosynthetic Pathway Is Related to the Heme-Dependent Dioxygenase Superfamily . Biochemistry . en . 46 . 43 . 12393–12404 . 10.1021/bi7012189 . 0006-2960 . 3326534 . 17924666.
6. Book: Pillonel. Ch. Encyclopedia of Agrochemicals. Knauf-beiter. G.. Steinemann. A.. 2003. 10.1002/047126363X.agr106. Fungicides, Phenylpyrroles. 047126363X.
7. Jespers. A.B.K.. Davidse. L.C.. Dewaard. M.A.. Biochemical Effects of the Phenylpyrrole Fungicide Fenpiclonil in Fusarium sulphureum (Schlecht). Pesticide Biochemistry and Physiology. 45. 2. 1993. 116–129. 0048-3575. 10.1006/pest.1993.1014.