Phosphinothricin

Uses

Glufosinate, a phosphinic acid analogue of glutamic acid, is a herbicide which is converted by plant cells into PT (L-phosphinothricin). Glufosinate exerts neurotoxic activity[1][2].

Production Methods

Glufosinate is commercially produced through microbial fermentation using genetically engineered Streptomyces species, followed by chemical purification and salt formation. The process begins with the cultivation of Streptomyces hygroscopicus or related strains that biosynthesise glufosinate as a secondary metabolite. Fermentation is carried out under controlled conditions in large bioreactors, where the organism produces the active compound over several days. After fermentation, the broth is filtered and the glufosinate is extracted and purified using ion-exchange chromatography and crystallisation.

Definition

ChEBI: 2-amino-4-[hydroxy(methyl)phosphoryl]butanoic acid is a non-proteinogenic alpha-amino acid that is 2-aminobutanoic acid which is substituted at position 4 by a hydroxy(methyl)phosphoryl group. It is a member of phosphinic acids and a non-proteinogenic alpha-amino acid.

Mechanism of action

Non-selective, contact with some systemic action. Glutamine synthetase inhibitor: accumulates ammonium ions, inhibits photosynthesis.

in vivo

Enzyme inhibitor

This dephospho transition-state analogue (FW = 177.10 g/mol; CAS 51276- 47-2) is naturally occurring glutamate analogue, first isolated from Streptomyces viridochromogenes. Phosphonothricin is a slow, tight-binding inhibitor of glutamine synthetase that binds at the glutamate binding site and stabilizes the flap of a glutamyl residue in a position blocking glutamate entry into the active site, thereby trapping the inhibitor on the enzyme. Phosphinothricin undergoes an ATP-dependent phosphorylation. Note: Phosphinothricin is a component of the antibiotics bialaphos and phosalacine. The monoammonium salt of the racemic compound, also called glufosinate-ammonium, is a post-emergent herbicide.

Metabolic pathway

When 14C-phosphinothricin [homoalanin-4-yl- (methyl)phosphinic acid] is incubated in the cell suspension cultures of soybean, wheat, and maize, in maize cells which take up to 50% of the applied radioactivity, four different metabolites are detected which are identified as 4-methylphosphinico-2-oxo- butyric acid, 4-methylphosphinico-2-hydroxybutyric acid, 4-methylphosphinicobutyric acid, and 3- methylphosphinicopropionic acid. In soybean and wheat cultures, 10 and 6% of the applied radioactivity is taken up, respectively. In soybean, only one metabolite, 3-methylphosphinicopropionic acid, is detected, whereas in wheat, 4-methyl- phosphinicobutyric acid is additionally present.

References

[1] áy Z, et al. The effect of high concentrations of glufosinate ammonium on the yield components of transgenic spring wheat (Triticum aestivum L.) constitutively expressing the bar gene. ScientificWorldJournal. 2012;2012:657945. DOI:10.1100/2012/657945
[2] Feat-Vetel J, et al. Multiple effects of the herbicide glufosinate-ammonium and its main metabolite on neural stem cells from the subventricular zone of newborn mice. Neurotoxicology. 2018 Dec;69:152-163. DOI:10.1016/j.neuro.2018.10.001
[3] Ebert E, et al. Summary of safety evaluation toxicity studies of glufosinate ammonium. Food Chem Toxicol. 1990 May;28(5):339-49. DOI:10.1016/0278-6915(90)90108-y

Pesticide Type

Herbicide