Acid-ammonia ligases

Acid-ammonia (or amine) ligases (amide synthetases)... 

Figure 3-4. The general phenylpropanoid pathway. The enzymes involved in this pathway are (a) phenylalanine ammonia lyase (PAL E.C. 4.3.1.5), (b) cinnamic acid 4-hydroxylase (C4H E.C. 1.14.13.11), and (J) 4-coumaric acid CoA ligase (4CL E.C. 6.2.1.12). (a) depicts tyrosine ammonia lyase activity in PAL of graminaceous species. The grey structures in the box represent an older version of the phenylpropanoid pathway in which the ring substitution reactions were thought to occur at the level of the hydroxycinnamic acids and/or hydroxycinnamoyl esters. The enzymes involved in these conversions are (c) coumarate 3-hydroxylase (C3H E.C. 1.14.14.1), (d) caffeate O-methyltransferase (COMT EC 2.1.1.68), (e) ferulate 5-hydroxylase (F5H EC 1.14.13), and (g) caffeoyl-CoA O-methyltransferase (CCoA-OMT EC 2.1.1.104). These enzymes are discussed in more detail in Section 10.

Coumaroyl-CoA is produced from the amino acid phenylalanine by what has been termed the general phenylpropanoid pathway, through three enzymatic conversions catalyzed by phenylalanine ammonia-lyase (PAL), cinnamate 4-hydroxylase (C4H), and 4-coumarate CoA ligase (4CL). Malonyl-CoA is formed from acetyl-CoA by acetyl-CoA carboxylase (ACC) (Figure 3.2). Acetyl-CoA may be produced in mitochondria, plastids, peroxisomes, and the cytosol by a variety of routes. It is the cytosolic acetyl-CoA that is used for flavonoid biosynthesis, and it is produced by the multiple subunit enzyme ATP-citrate lyase that converts citrate, ATP, and Co-A to acetyl-CoA, oxaloacetate, ADP, and inorganic phosphate. ... 

Figure 1.35 Schematic diagram of the phenolic biosynthetic pathway accompanied by the key enzymes involved. Enzyme abbreviations PAL, phenylalanine ammonia-lyase BA2H, benzoic acid 2-hydroxylase C4H, cinnamate 4-hydroxylase COMT-1, caffeic/5-hydroxyferulic acid O-methy I transferase 4CL, p-co um a ra te C o A ligase F5H, ferulate 5-hydroxylase GT, galloyltransferase ACoAC, acetylCoA carboxylase.

The enc cluster contains four genes (encH, encl, encJ, encP) involved in the biosynthesis of the unusual benzoyl-CoA (185) starter from phenylalanine (186) via a plant-like p-oxidation mechanism (Fig. 32) [208-210]. This pathway is initiated by the unique phenylalanine ammonia-lyase EncP [211], which catalyzes the generation of cinnamic acid (187) from 186. The cinnamate-CoA ligase EncH... 

Phenylalanine ammonia-lyase (PAL) eliminates the amino group from phenylalanine (12) to produce cinnamic acid (13). Cinnamate-4-hydroxylase (C4H) hydroxidizes compound (13) to yield p-coumaric acid (14). 4-CoumaroyhCoA-ligase (4CL) complex catalyzed the conversion of p-coumaric acid (14) and coenzyme A (CoA) to 4-coumaroyl-CoA (15) and 3 moles malonyl-CoA (16). Stilbene synthase (STS) converts these two compounds (15,16) into resveratrol of stilbene (7) (Fig. 3) [23,24],... 

Biosynthesis of flavonoids starts with the conversion of phenylalanine or tyrosine to cinnamic acid by phenylalanine ammonia lyase (PAL) (Hahlbrock and Grisebach, 1975). Subsequent reactions are catalyzed by cinnamic acid 4-hydrolase to form 4-hydroxyl cinnamic acid (p-coumaric acid). The p-coumaric acid is then catalyzed by p-coumarate CoA ligase to form p-coumaroyl CoA. 

Figure 3.1 Primary flux of carbon through phenylpropanoid pathway in Arabidopsis. PAL, phenylalanine ammonia-lyase 4CL, 4-(hydroxy)cinnamoyl CoA ligase C4H, cinnamate 4-hydroxylase HCT, hydroxycinnamoyl-CoA shikimate/quinate hydroxycinnamoyltransferase C3 H, /7-coumaroylshikimate 3 -hydroxylase CCoAOMT, caffeoyl CoA O-methyltransferase F5H, ferulate 5-hydroxylase COMT, caffeic acid/5-hydroxyferulic acid o-methyltransferase CCR, cinnamoyl CoA reductase CAD, cinnamyl alcohol dehydrogenase. Not depicted is the HCT catalyzed synthesis of/r-coumaroyl quinate.

The biosynthetic pathway for isoflavonoids in soybean and the relationship of the isoflavonoids to several other classes of phenylpropanoids is presented in Fig. 8.2. Production of /i-coumaryl-CoA from phenylalanine requires phenylalanine ammonia lyase to convert phenylalanine to cinnamate, cinnamic acid hydroxylase to convert cinnamate to /7-coumarate, and coumaraterCoA ligase to convert jt -coumarate to -coumaroyl-CoA. Lignins may be produced from j3-coumaroyl-CoA or from />-coumarate. Chalcone synthase catalyzes the condensation of three molecules of malonyl CoA with p-coumaroyl-CoA to form 4, 2 , 4 , 6 -tetrahydroxychalcone, which is subsequently isomerized in a reaction catalyzed by chalcone isomerase to naringenin, the precursor to genistein, flavones, flavonols, condensed tannins, anthocyanins, and others. 

The first step of flavonone biosynthesis begins with the deamination of the amino acid phenylalanine or tyrosine by a phenylalanine ammonia-lyase (PAL) or a tyrosine ammonia-lyase (TAL), which affords cinnamic acid and p-coumaric acid, respectively (Figure 6.36). The formed cinnamic acid is first hydroxylated to p-coumaric acid by a membrane-bound P450 monooxygenase, cinnamate 4-hydroxylase (C4H), and then activated to p-coumaroyl-CoA by a 4-coumarate-CoA ligase (4CL). 4CL catalyzes also the conversion of caffeic acid, feruhc acid, and cinnamic acid to caffeoyl-CoA, feruloyl-CoA, and cinnamoyl-CoA, respectively. 

Resveratrol biosynthesis branches from the phenylpropanoid pathway. The resveratrol biosynthesis pathway consists of four enzymesrphenylalanine ammonia lyase (PAL), cinnamic acid 4-hydroxylase (C4H), 4-coumarate CoA ligase (4CL), and stilbene synthase (STS). The first two enzymes of the pathway, PAL and C4H, convert phenylalanine into /)-coumaric acid. The third enzyme, 4CL, attaches /)-coumaric acid to the pantetheine group of coenzyme-A (CoA) to produce 4-coumaroyl-CoA. The fourth enzyme, STS, catalyzes the condensation of resveratrol from one molecule of 4-coumaroyl-CoA and three molecules of malonyl-CoA, which originate from fatty acid biosynthesis. TAL is homologous to PAL and converts the amino acid tyrosine directly into / -coumaric acid. Methylated resveratrol derivatives of pinostilbene and pterostilbene are produced by resveratrol O-methyltransferase (ROMT) from resveratrol [135] (Figure 10.10). 

An alternate fate of the products of photosynthesis that are channeled through the shikimate pathway is for 3-dehydroshikitnic acid to be directed to L-phenylalanine and so enter the phenylpropanoid pathway (Figure 1.15). Phenylalanine ammonia-lyase catalyses the first step in this pathway, the conversion of L-phenylalanine to cinnamic acid, which in a reaction catalysed by cinnamate 4-hydroxylase is converted to p-coumaric acid which in turn is metabolized to p-coumaroyl-CoA by p-coumarate CoA ligase. Cinnamic add is... 

PAL, phenylalanine ammonia lyase CA4H, cinnamic acid 4-hydroxylase CPR, Cytochrome P450 reductase 4CL, 4-coumaroyl-CoA ligase CA3H, coumaric add 3-hydroxylase COMT, caffeicacid O-methyltransferase SAM, S-adenosyl-methionine HCHL, hydroxycinnamoyl-CoA pAMT, putative aminotransferase AA, amino add KA, Keto add... 

---