Amino acids lyases

Watts KT, Mijts BN, Lee PC, Manning AJ, Schmidt-Dannert C (2006) Discovery of a substrate selectivity switch in tyrosine ammonia-lyase, a member of the aromatic amino acid lyase family. Chem Biol 13(12) 1317-1326... 

Combined use of microbial enzymes as biocatalysts with chemical synthesis has its origin in the steroid transformation developed in the USA in the early 1950s. Arima and his group [11] invented a unique microbial conversion process, in which the aliphatic side-chain of cholesterol was cleaved to produce a steroid core as a starting material for chemical synthesis of steroid hormones. Yamada et al. discovered the reverse reaction of the pyridoxal-containing L-amino acid lyases and applied them to synthesize L-tryptophan and l-DOPA [12] from pyruvate, ammonia and corresponding aromatic compounds. Since these early achievements, a variety of unique processes with newly screened microbial enzymes as biocatalysts have been invented. 

The acetyl-CoA derived from amino acid degradation is normally insufficient for fatty acid biosynthesis, and the acetyl-CoA produced by pyruvate dehydrogenase and by fatty acid oxidation cannot cross the mitochondrial membrane to participate directly in fatty acid synthesis. Instead, acetyl-CoA is linked with oxaloacetate to form citrate, which is transported from the mitochondrial matrix to the cytosol (Figure 25.1). Here it can be converted back into acetyl-CoA and oxaloacetate by ATP-citrate lyase. In this manner, mitochondrial acetyl-CoA becomes the substrate for cytosolic fatty acid synthesis. (Oxaloacetate returns to the mitochondria in the form of either pyruvate or malate, which is then reconverted to acetyl-CoA and oxaloacetate, respectively.)... 

A subclass of lyases, involved in amino acid metabolism, utilizes pyridoxal 5-phosphate (PLP, 3-hydroxy-2-methyl-5-[(phosphonooxy)methyl]-4-pyridinecarbaldehyde) as a cofactor for imine/ enamine-type activation. These enzymes are not only an alternative to standard fermentation technology, but also offer a potential entry to nonnatural amino acids. Serine hydroxymethyl-tansferase (SHMT EC 2.1.2.1.) combines glycine as the donor with (tetrahydrofolate activated) formaldehyde to L-serine in an economic yield40, but will also accept a range of other aldehydes to provide /i-hydroxy-a-amino acids with a high degree of both absolute and relative stereochemical control in favor of the L-erythro isomers41. 

Inherited defects in the enzymes of (3-oxidation and ketogenesis also lead to nonketotic hypoglycemia, coma, and fatty hver. Defects are known in long- and short-chain 3-hydroxyacyl-CoA dehydrogenase (deficiency of the long-chain enzyme may be a cause of acute fetty liver of pr nancy). 3-Ketoacyl-CoA thiolase and HMG-CoA lyase deficiency also affect the degradation of leucine, a ketogenic amino acid (Chapter 30). 

Oxidoreductases Transferases Hydrolases Lyases Isomerases Ligases Phenolic polymers, polyanilines, vinyl polymers Polysaccharides, cyclic oligosaccharides, polyesters Polysaccharides, polyesters, polycarbonates, poly(amino acid)s, polyphosphates... 

The PelX protein contains 749 amino-acids including an amino-terminal signal sequence of 26 amino-adds. The celliilar localisation of the enzyme has not been rigorously determined. In E. chrysanthemi CUCPB1237, the exo-pectate lyase activity was cell-bound (14). The presence of this type of enzyme in the bacterial periplasm appeared normal since it acts better on oligomers produced by endo-pectate lyases than on long polymeric substrates (15). 

Recently, a new pectate lyase gene pelZ, was identified at the vicinity of the pelB-pelC cluster (Pissavin et al, submitted). ApelZ homologue was also foimd in Erwinia carotovora. PelZ defines a new family of endo-pectate lyase since its amino acid sequence displays only very low homology with that of other pectinases. 

Fig. 1. Schematic overview of Aspergillus niger pectin lyase genes pel A to pelF aa, amino acid m.p. mature protein.

Phenylalanine ammonia-lyase (PAL EC 4.3.1.5) is a pivotal enzyme in controlling flow of carbon from aromatic amino acids to secondary aromatic compounds (Figure 1) (28). PAL primarily deaminates phenylalanine to form t-cinnamic acid, however, in many species, it also less efficiently deaminates tyrosine to form -coumaric acid. Because PAL is restricted to plants and is an important enzyme in plant development, Jangaard (29) suggested that PAL inhibitors might make safe and effective herbicides, however, in his screen of several herbicides, he found no compound to have a specific effect on PAL. This was also the case in studies by Hoagland and Duke (30, 31.) in which 16 herbicides were screened. 

Hydroxynitrile lyases (HNLs or oxynitrilases) catalyze C—C bond-forming reactions between an aldehyde or ketone and cyanide to form enantiopure cyanohydrins (Figure 1.15), which are versatile building blocks for the chiral synthesis of amino acids, hydroxy ketones, hydroxy acids, amines and so on [68], Screening of natural sources has led to the discovery of both... 

Sulfur-containing amino acids, especially L-methionine, serve as precursors for MT and the many materials derived from this compound, such as DMS, DMDS, DMTS, methyl thioacetate, etc. The most direct route for the L-methionine MT conversion is by demethiolation (Equation 4) catalyzed by methionine y-lyase, EC 4.4.1.11 ... 

The first structures of this kind were reported in 1993 pectate lyase G from Erwinia chrysanthemi (Yoder et al, 1993) and alkaline protease from Pseudomonas aeruginosa (Baumann et al, 1993). Based on consideration of these crystal structures, the term parallel //-helix was introduced for a fold containing three //-strands per coil, and parallel //-roll for a fold with two //-strands per coil (Baumann etal, 1993 Yoder andjurnak, 1995 Yoder et al., 1993). The epithet parallel was intended to emphasize the distinction between these folds and the previously observed helical structure of the antibiotic gramicidin which contains both l- and D-amino acids and... 

The realization of the widespread occurrence of amino acid radicals in enzyme catalysis is recent and has been documented in several reviews (52-61). Among the catalytically essential redox-active amino acids glycyl [e.g., anaerobic class III ribonucleotide reductase (62) and pyruvate formate lyase (63-65)], tryptophanyl [e.g., cytochrome peroxidase (66-68)], cysteinyl [class I and II ribonucleotide reductase (60)], tyrosyl [e.g., class I ribonucleotide reductase (69-71), photosystem II (72, 73), prostaglandin H synthase (74-78)], and modified tyrosyl [e.g., cytochrome c oxidase (79, 80), galactose oxidase (81), glyoxal oxidase (82)] are the most prevalent. The redox potentials of these protein residues are well within the realm of those achievable by biological oxidants. These redox enzymes have emerged as a distinct class of proteins of considerable interest and research activity. 

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