Interaction of tyrosine phenol-lyase with phosphoroorganic analogues of substrate amino acids

Abstract

The phosphinic analogues of tyrosine and pyruvate were first demonstrated to be substrates in the reactions of elimination and synthesis catalyzed by tyrosine phenol-lyase. Kinetic parameters of the enzymatic process were determined, and the first enzymic synthesis of an aminophosphinic acid was carried out. Replacement of the planar HOOC-group by the tetrahedral (HO)(O)PH-group in the substrate slightly affected its affinity for the enzyme but substantially diminished the conversion rate. For phosphonic analogues, containing (HO) 2 (O)P group, the affinity to the enzyme was decreased considerably while the conversion was completely prevented. Thus, the structural parameters of the acid group are important not only for the affinity for the enzyme, but also for the formation of the catalytically competent conformation of the active site.

Crystallographic Snapshots of Tyrosine Phenol-lyase Show That Substrate Strain Plays a Role in C–C Bond Cleavage

“…4.1.99.2) is a pyridoxal 5′-phosphate (PLP)-dependent enzyme, which catalyzes the reversible cleavage of the Cβ–Cγ bond of l -Tyr to produce phenol, ammonium, and pyruvate (Scheme ). In addition to its physiological reaction, in vitro TPL catalyzes a plethora of other reactions including β-elimination (and its reversal) of a number of other α-amino acids and several structurally similar compounds, as well as β-substitutions by phenol derivatives and their heterocyclic analogues . Some of these TPL-catalyzed reactions have been utilized for biotechnological production of l -Tyr and several related compounds like l -DOPA, a top-selling drug prescribed for treatment of Parkinson’s disease .…”

Chemoenzymatic synthesis of optically active phosphinic analogues of S-substituted sulfur-containing amino acids

“…5 The prospects of using enzymatic methods for the separation and/or synthesis of chiral phosphinic analogues of amino acids were first demonstrated by the example of interaction of the enantiomers of a tyrosine phosphinic analogue with PLP-dependent L-tyrosinephenol-lyase. 3 Thus, only (R)-isomer of the phosphinic acid, whose configuration corresponds to natural (S)-tyrosine, proved to be the substrate in the reaction of α,β-elimination. Accordingly, (R)-isomer of the tyrosine phosphinic analogue was the product of the reverse enzymatic reaction.…”

“…1-Aminoalkylphosphinic acids, analogues of natural α-amino acids, display pronounced biological activity and are extensively applied in enzymological studies. [1][2][3] However, only a few optically active compounds of this kind have been obtained until now. Thus, (R)-isomers of phosphinic analogues of alanine and phenylalanine have previously been prepared by the stereoselective alkylation of chiral Schiff bases derived from (1R,2R,5R)-2-hydroxypinan-3-one and the ethyl esters of aminomethyl-(diethoxymethyl)phosphinic acid by methyl iodide and benzyl chloride, respectively, while the stereoselectivity of the reaction strongly depended on the structure of the alkyl halide.…”