Draft:Phaseolotoxin

Phaseolotoxin
Chemical structure of phaseolotoxin
Names
IUPAC name
(2S)-2-[[(2S)-2-[[(2S)-2-amino-5-[[amino-(sulfoamino)phosphoryl]amino]pentanoyl]amino]propanoyl]amino]-6-(diaminomethylideneamino)hexanoic acid
Identifiers
3D model (JSmol)
ChemSpider
KEGG
UNII
  • Key: QDAOSMKOZCCWLJ-MQLLGTBWSA-N
  • InChI=1S/C15H34N9O8PS/c1-9(12(25)23-11(14(27)28)6-2-3-7-20-15(17)18)22-13(26)10(16)5-4-8-21-33(19,29)24-34(30,31)32/h9-11H,2-8,16H2,1H3,(H,22,26)(H,23,25)(H,27,28)(H4,17,18,20)(H,30,31,32)(H4,19,21,24,29)/t9-,10-,11-/m0/s1
  • C[C@@H](C(=O)N[C@@H](CCCCN=C(N)N)C(=O)O)NC(=O)[C@H](CCCNP(=O)(N)NS(=O)(=O)O)N
Properties
C15H34N9O8PS
Molar mass 531.53 g·mol−1
Appearance White to off-white solid
Melting point Decomposes upon heating
Soluble
Hazards
Occupational safety and health (OHS/OSH):
Main hazards
 Phytotoxin; inhibitor of ornithine carbamoyltransferase
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Tracking categories (test):

Phaseolotoxin is a naturally occurring phytotoxin produced by the bacterium Pseudomonas syringae pv. phaseolicola. It was first characterized in the late 1960s and 1970s during investigations into the cause of the distinctive yellow halos surrounding necrotic lesions on infected bean leaves of the common green bean (Phaseolus vulgaris).[1] These lesions are symptoms of halo blight and are mostly caused by the activity of phaseolotoxin, diffusing from bacterial infection sites into surrounding plant tissue.[2] Its name is derived from the genus Phaseolus, reflecting its association with halo blight.

On a molecular level, phaseolotoxin interferes with plant nitrogen metabolism by inhibiting ornithine carbamoyltransferase (OCTase), which is a key enzyme in the arginine biosynthesis pathway.[3] Inhibition of this enzyme leads to a decreased level of arginine in plant cells, which further results in metabolic imbalance, chlorosis, and weakened plant growth. Phaseolotoxin has become an important model compound for studying toxin-mediated plant-pathogen interactions due to its well defined molecular target.

Chemical properties

Phaseolotoxin is a peptide-derived phytotoxin consisting of a modified tripeptide linked to an unusual phosphosulfamyl functional group.[4] This chemical group structurally resembles the transition state of carbamoyl phosphate–dependent reactions catalyzed by OTCase, allowing the toxin to bind strongly to the enzyme’s active site.

The molecule contains a tripeptide backbone composed of ornithine, alanine, and homoarginine residues. The phosphosulfamyl group attached to the ornithine residue is essential for the inhibitory activity of the toxin.

The presence of this rare functional group differentiates phaseolotoxin from most other peptide toxins and is responsible for its high affinity toward its enzymatic target.[4]

Structure and reactivity

An important structural feature of phaseolotoxin is the N-sulfodiaminophosphinyl group attached to the ornithine residue. This part behaves as a transition state analog, mimicking intermediates involved in carbamoyl phosphate–dependent enzymatic reactions.[4]

Due to this structural similarity, phaseolotoxin binds strongly to the active site of ornithine carbamoyltransferase and hereby inhibiting its catalytic activity. The phosphosulfamyl group also exhibits moderate chemical reactivity and hydrolytic cleavage can occur under physiological conditions.

Part of the peptide backbone of phaseolotoxin is removed during enzymatic processing after entering plant tissues. This reaction produces N-phosphosulfamyl-ornithine (PSOrn), which acts as the active inhibitor of ornithine carbamoyltransferase.[3]

Biosynthesis

The biosynthesis of phaseolotoxin occurs in Pseudomonas syringae pv. phaseolicola and is encoded by the argK-tox gene cluster located on the bacterial chromosome.[5] This gene-cluster contains more than twenty genes involved in toxin production, including enzymes responsible for amino acid modification, peptide assembly, phosphorylation, sulfur transfer reactions, and toxin transportation.

The biosynthetic pathway begins with common amino acid precursors, particulary ornithine, which undergoes enzymatic modification to generate the unusual phosphosulfamyl-containing intermediate. Additional enzymatic reactions incorporate alanine and homoarginine residues to form the tripeptide backbone of the toxin. After synthesis, specialized transport proteins distribute phaseolotoxin from the bacterial cell into the surrounding plant tissue.[5]

To prevent self-intoxication, the bacterium expresses the argK gene, which encodes a modified form of OTCase that is resistant to inhibition by phaseolotoxin. This resistance mechanism allows the bacterium to maintain its own arginine biosynthesis while producing the toxin.

Production of phaseolotoxin is strongly influenced by environmental conditions, particularly temperature. Maximum toxin production occurs at relatively low temperatures between 18 and 22 °C, conditions that also favor halo blight outbreaks in agricultural field.[2][failed verification][6]

Metabolism and mode of action

Within plant tissues, metabolic conversion of phaseolotoxin occurs into the active inhibitor N-phosphosulfamyl-ornithine (PSOrn) after cleavage of the peptide portion of the molecule.[3]

PSOrn acts as a competitive inhibitor of OTCase. Generally this enzyme catalyzes the conversion of ornithine and carbamoyl phosphate into citrulline, an intermediate in arginine biosynthesis.

Normal arginine production is blocked by the inhibitor by binding to the enzymes active site and mimicking the natural substrate, blocking the catalytic reaction.[3] As arginine levels decrease, several cellular processes (including protein synthesis, nitrogen metabolism, and polyamine biosynthesis) become disrupted. This results in chlorosis and the characteristic yellow halo surrounding infected lesions due to metabolic imbalance.

Role in plant-pathogen interactions

Phaseolotoxin functions as a major virulence factor of Pseudomonas syringae pv. phaseolicola. After secretion by the bacterium, the toxin diffuses through leaf tissue beyond the immediate infection site.[2]

This diffusion explains the formation of chlorotic halos surrounding necrotic lesions in infected bean leaves. By disrupting arginine biosynthesis and nitrogen metabolism, the toxin weakens plant physiological functions and may impair plant defense responses, facilitating further bacterial colonization.

Agricultural impact

Halo blight is an economically important disease affecting bean cultivation worldwide. Severe outbreaks typically occur under cool and humid conditions that favor both bacterial growth and toxin production.[2]

Typical disease symptoms include chlorotic halos around lesions, necrotic leaf spots, reduced photosynthetic activity, and decreased plant growth. Management strategies include the use of resistant varieties, certified disease-free seeds, crop rotation, and improved field hygiene

Toxicology and research applications

Phaseolotoxin is mainly investigated in plant pathology, but because of its ability to disrupt the metabolism of amino acids, it has also drawn attention in biomedical research..

Phaseolotoxin has been shown in experiments to suppress the growth of the pancreatic insulinoma cell line RIN-m5F and a number of leukemia cell lines, including HL-60, K-562, and L1210.[7] The inhibitory effects occur in a dose-dependent manner with reported IC50 values between approximately 2 and 13 μM, depending on the cell line.

These effects may be related to interference with enzymes involved in polyamine biosynthesis, a pathway that plays an important role in cell growth. Because of these properties, phaseolotoxin has been investigated as a potential lead compound in anticancer drug research, although further studies are required to evaluate its safety and therapeutic potential.[7]

References

  1. ^ Mitchell, Robin E. (1976). "Isolation and structure of a chlorosis-inducing toxin of Pseudomonas phaseolicola". Phytochemistry. 15 (12): 1941–1947. doi:10.1016/s0031-9422(00)88851-2.
  2. ^ a b c d Mansfield, John; Genin, Stephane; Magori, Shimpei; Citovsky, Vitaly; Sriariyanum, Malinee; Ronald, Pamela; Dow, MAX; Verdier, Valérie; Beer, Steven V.; Machado, Marcos A.; Toth, IAN; Salmond, George; Foster, Gary D. (2012). "Top 10 plant pathogenic bacteria in molecular plant pathology". Molecular Plant Pathology. 13 (6): 614–629. doi:10.1111/j.1364-3703.2012.00804.x. PMC 6638704. PMID 22672649.
  3. ^ a b c d Templeton, M. D.; Sullivan, P. A.; Shepherd, M. G. (1984). "The inhibition of ornithine transcarbamoylase from Escherichia coli W by phaseolotoxin". Biochemical Journal. 224 (2): 379–388. doi:10.1042/bj2240379. PMC 1144443. PMID 6393952.
  4. ^ a b c Bender, Carol L.; Alarcón-Chaidez, Francisco; Gross, Dennis C. (1999). "Pseudomonas syringae Phytotoxins: Mode of Action, Regulation, and Biosynthesis by Peptide and Polyketide Synthetases". Microbiology and Molecular Biology Reviews. 63 (2): 266–292. doi:10.1128/mmbr.63.2.266-292.1999. PMC 98966. PMID 10357851.
  5. ^ a b Zhang, Y.; Rowley, K. B.; Patil, S. S. (1993). "Genetic organization of a cluster of genes involved in the production of phaseolotoxin, a toxin produced by Pseudomonas syringae pv. Phaseolicola". Journal of Bacteriology. 175 (20): 6451–6458. doi:10.1128/jb.175.20.6451-6458.1993. PMC 206753. PMID 8407821.
  6. ^ Murillo J, de Ingenieros PE, Bardaji L, de Ingenieros PE, Führer ME, de Ingenieros PE (December 2010). "La grasa de las judías, causada por la bacteria Pseudomonas syringae pv. phaseolicoda" [The halo blight of beans, caused by Pseudomonas syringae pv. phaseolicoda bacteria]. Phytoma España (in Spanish) (224): 27–32. ISSN 1131-8988. Archived from the original on 2022-01-25. Así, en presencia de una adecuada fuente de inóculo, las mayores pérdidas se producen con ... y con temperaturas moderadas (18-22ºC). ... Después, y a temperaturas que ronden los 16-22ºC, es frecuente que las lesiones aparezcan rodeadas de un halo ... que se debe a la acción de una toxina producida por el patógeno, la faseolotoxina. ... Las temperaturas superiores a, aproximadamente, 24ºC inhiben la producción de faseolotoxina y, por tanto, conducen a la producción de síntomas sin el halo característico.
  7. ^ a b Bachmann, André S.; Xu, Ronghui; Ratnapala, Lal; Patil, Suresh S. (2004). "Inhibitory effects of phaseolotoxin on proliferation of leukemia cells HL-60, K-562 and L1210 and pancreatic cells RIN-m5F". Leukemia Research. 28 (3): 301–306. doi:10.1016/j.leukres.2003.07.002. PMID 14687626.

Category:Tripeptides Category:Toxins Category:Sulfonamides

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