Homology Modeling of Mio-dependent Ammonia- Lyases and 2,3-aminomutases - Mechanistic Comparisons

Aromatic ammonia-lyases catalyze the non-oxidative ammonia elimination from aromatic Lamino-acids, producing α,β-unsaturated compounds. The members of this enzyme family are the phenylalanine ammonia-lyase (PAL, EC 4.3.1.24), (Hodgins, 1971) histidine ammonia-lyase (HAL, EC 4.3.1.3) (Givot et al., 1969; Wickner, 1969) and the tyrosine ammonia-lyase (TAL, EC 4.3.1.23) (Kyndt et al., 2002) catalyzing the deamination of the corresponding L-amino acids to (E)-cinnamic acid, (E)-urocanic acid and (E)-coumaric acid respectively, as shown in Fig. 1. In plants PAL catalyses the first step of the phenylalanine degradation pathway, and thus the biosynthesis of several classes of phenylpropanoids, such as lignins, flavonoids and coumarins (Hanson and Havir, 1978). The synthetic application of PAL is based on the stereoconstructive reverse reaction yielding L-phenylalanine derivatives from achiral precursors or the kinetic resolution of racemic amino acids providing access to D-phenylalanine derivatives as residual substrates (Poppe and Rétey, 2003). From an environmental point of view it is important that PAL lies at the branch of primary and secondary metabolism in plants and therefore it is a target for herbicides (Poppe and Rétey, 2005).