Phenylalanine aminomutase

The studies on the synthesis and installation of the side chain held a particular surprise. The phenylpropanoyl residue stems from phenylalanine, not from cinnamic acid. (L)-Phenylalanine is converted into phenyl-yS-alanine by means of phenylalanine-aminomutase, and then hydroxylated, followed by esterification with baccatin III. In the final step of the paditaxel biosynthesis, this ester is converted into the amide. Interestingly, the benzamide is essential for the pharmacological activity of paditaxel. 

On the other hand, the biocatalytic enantioselective addition of hydrazine, hydroxylamine, methoxylamine, and methylamine to fiimarate has been described employing aspartate ammonia lyase [97]. Other enzyme-catalyzed procedures include the addition of ammonia to substituted cinnamic acids employing phenylalanine aminomutase [98, 99]. 

In a related fashion, asymmetric amination of ( )-cinnamic acid yields L-phenylalanine using L-phenylalanine ammonia lyase [EC 4,3,1,5] at a capacity of 10,000 t/year [1274, 1601], A fascinating variant of this biotransformation consists in the use of phenylalanine aminomutase from Taxus chinensis (yew tree), which interconverts ot- to p-phenylalanine in the biochemical route leading to the side chain of taxol [1602], In contrast to the majority of the cofactor-independent C-0 and C-N lyases discussed above, its activity depends on the protein-derived internal cofactor 5-methylene-3,5-dihydroimidazol-4-one (MIO) [1603], Since the reversible a,p-isomerization proceeds via ( )-cinnamic acid as achiral intermediate, the latter can be used as substrate for the amination reaction. Most remarkably, the ratio of a- vs, 3-amino acid produced (which is 1 1 for the natural substrate, R = H) strongly depends on the type and the position of substituents on the aryl moiety While o-substituents favor the formation of a-phenylalanine derivatives, / -substituted substrates predominantly lead to p-amino analogs, A gradual switch between both pathways occurred with m-substituted compounds. With few exceptions, the stereoselectivity remained exceUent (Scheme 2,215) [1604, 1605],... 

In 2010, Janssen and co-workers reported that the kinetic resolution of p-phenylalanine catalysed by a tandem biocatalytic system composed of phenylalanine aminomutase (PAM) and phenylalanine ammonia lyase (PAL) yielded the corresponding enantiopure (5)-p-phenylalanine in good yield (48%) and excellent enantiomeric excess of >99% ee (Scheme 4.13). The process was based upon the PAM-catalysed, reversible, enantioselective transformation of (I )-p-phenylalanine to (S)-a-phenylalanine. The latter one was transformed in a PAL-catalysed regioselective process into ( )-cinnamic acid, with liberation of ammonia. This constituted an example of a tandem biocatalytic, kinetic resolution in which one enzyme catalysed the equilibration between the substrate and reaction intermediate, while the other shifted this equilibrium between the substrate towards the final product... 

KYNURENINE AMINOTRANSFERASE LEUCINE AMINOTRANSFERASE LYSINE 2,3-AMINOMUTASE LYSINE 6-AMINOTRANSFERASE LYSINE DECARBOXYLASE METHIONINE y-LYASE ORNITHINE AMINOTRANSFERASE PHENYLALANINE DECARBOXYLASE PHOSPHATIDYLSERINE DECARBOXYLASE... 

Biosynthesis of (R)-/f-Phenylalanine in Taxus baccata The biosynthesis of the (R)-3-(dimethylamino)-3-phenylpropionic acid (Wintersteirfs acid) moiety of taxine A [56] and taxine B [57] in Taxus baccata has been reported by Haslam and coworkers [58]. They investigated whether /(-phenylalanine is generated by an aminomutase... 

These experiments do not, nevertheless, enable conclusions to be drawn about which of the hydrogen atoms at C3 is transferred to C2. It therefore remains an open question whether the mutase of the mushroom resembles more the phenylalanine 2,3-aminomutase from Taxus brevifolia or the lysine 2,3-aminomutase from Clostridium subterminale SB4. Because of the lack of any evidence of the occurrence of B12 in higher fungi [65], involvement of B12 in the aminomutase reaction is unlikely. 

Interestingly, all known cobalamin-dependent aminomutases seem to catalyze a shift of the co amino group whereas the SAM dependent lysine 2,3-aminomutase catalyzes the shift of the a amino group. The latter is true for phenylalanine 2,3-aminomutase in Taxus brevifolia and tyrosine 2,3-aminomutase in Cortinarius vio-... 

The latter may be envisaged as an intermediate in the degradation of phenylalanine. In Clostridia catabolic breakdown of lysine (37) occurs by initial conversion to 6-lysine (38), (mediated by a 2,3-aminomutase) and thence via 3-keto-5-aminohexanoate to acetate and butyrate. An analogous catabolic sequence commencing with phenylalanine would lead to benzoic acid (as its CoA ester) and acetoacetate with the 6-aminophenylalanine (39) as an intermediate (Fig. 6). 

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