Amino-mutases

P. A. Frey, C. H. Chang, Amino-mutases in Chemistry and Biochemistry ofBi2, R. Banerjee, ed., Wiley, New York, 1999, pp. 835-857. For farther references on Frey s work see biosynthesis section. 

Recently, a new SAM dependent lysine 2,3-aminomutase was detected and characterized in Bacillus subtilis. Unlike the enzyme from C. subterminah SB4, the enzyme in B. subtilis apparently consists of four identical subunits each with a molecular mass of 54 kDa [30]. A PLP binding motif was identified in this amino-mutase that is also highly conserved in other lysine 2,3-aminomutases [31]. 

The amino mutases require pyridoxal phosphate for activity, and although little is known about them mechanistically, Freyis work on lysine 2,3-aminomutase has proved very informative (Lieder et al., 1998 Frey, 1997). Lysine 2,3-aminomutase is not a 1 2 enzyme but it functions very similarly (Section 1). The enzyme uses pyridoxal phosphate to facilitate the 1,2... 

About 10 coenzyme B -dependent enzymes are now known (reviewed in References 13,14, and 76 see Table 1) four carbon skeleton mutases (methylmalonyl-CoA mutase (MMCM), glutamate mutase (GM), methylene glu-tarate mutase (MGM), isobutyryl-CoA mutase (ICM) ), diol dehydratase (DD), glycerol dehydratase, ethanol-amine anunonia lyase (EAL), two amino mutases, and Bi2-dependent ribonucleotide reductase. The coenzyme Bi2-dependent enzymes are unevenly distributed in the living world, and MMCM is the only enzyme that is also indispensable in human metabolism. ... 

Reversible reactions that rearrange molecular skeletons (X is a carbon-based group in the carbon skeleton mutases and NH2 in the amino mutases X is shown in red below)... 

The second class of B12-dependent enzymes is represented by the aminomutases. All reactions in this class involve the 1,2-shift of an amino group. More often than not, the substrates involved in these transformations are the all-important a-amino acids. A typical such example is provided by L-leucine-2,3-amino mutase (reaction d in Scheme 2). 

Figure 14 Biosynthesis of PKS-NRPS hybrid compounds in myxobacteria (b). Biosynthesis of chondramide D (34) in Chondromyces crocatus Cm c5. The DH domain from module 1 (marked with an asterisk) is most likely inactive. During the assembly of the chondramide backbone, an unusual extender unit - a /3-amino acid - is incorporated by NRPS module 6. The precursor is generated by the tyrosine amino mutase (TAM) CmdF, which converts L-tyrosine into R-/3-tyrosine (see box). The function of the terminal phosphoenolpyruvate synthase (PEP) domain is still unknown. Macrocyclization catalyzed by the TE domain yields chondramide C (40), which can be further transformed to the chlorinated derivative chondramide D (34). The halogenation process catalyzed by CmdE may also take place on the assembly line intermediate.

Lysine 5,6-aminomutase (5,6-LAM) catalyzes the isomerization of D-lysine to 2,5-diaminohexanoic acid [180,181]. The mechanism proposed is analogous to that of D-ornithine amino mutase [228,229]. 5,6-LAM was predicted to be a base-off/His-on Bi2-dependent enzyme [230], as was recently conformed by the crystal structure [231]. 

In biochemical parlance, these systems are called mutases, or sometimes isomerases. When Z = OH and Y = OH or NHj, the product eliminates an aldehyde and either HjO or NH3 so that the process is irreversible. Such systems sometimes are referred to as eliminases, dehydrases or ammonia-lyases. Examples of these various types of systems are shown by the first five examples in Figure 8.3, where (CoA)—S represents coenzyme A. It should be noted that the amino mutases, such as ornithine amino mutase, also require pyridoxal phosphate as a cofactor. 

To emphasize some of the common features, these systems have been separated into three classes Class I are the mutases, such as glutamate mutase, in which a C—C bond is broken, and all exist in the base-off/hist-on form Class II are the eliminases which involve C—O or C—N bond cleavage and ribonuleotide triphosphate reductase, and are in the base-on form Class III are the amino mutases which interchange H and NH2 and require pyridoxal phosphate as a cofactor. The structure of one member of this class has b n determined and found to be in the base-off/hist-on form. The pyridoxal phosphate is covalently bonded to a lysine, Lys-NHj, of the peptide, as shown in the following reaction ... 

The search for optimum methods and conditions in the production of chiral amines is nowadays considered as a key issue for the industrial sector [178]. Traditionally, hydrolases have played a major role in this area [179,180], although other classes of enzymes such as amine dehydrogenases, monoamine oxidases, phenyl amino-mutases, and transaminases have opened a myriad of possibilities in this field [181,182]. 

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