CoA ligases

Scheme 10.32 Examples of reactions catalyzed by different classes of dehalogenases. HD haloalcohol dehalogenase EH epoxide hydrolase CL p-chlorobenzoyl-CoA ligase CBD p-chlorobenzoyl-CoA dehalogenase.

Kuhn, D.N., Chappell, J., Boudet, A. Hahlbrock, K. (1984). Induction of phenylalanine ammonia-lyase and 4-coumarate CoA ligase mRNAs in cultured plant cells by UV light or fungal elicitor. Proceedings of the National Academy of Sciences, USA, 81,1102-6. 

Fig. 12. Tentative model of the signal transduction chain that links the perception of pectic fragments to defense responses in carrot cells. Abbreviations apy, heterotrimeric G protein CaM, calmodulin 4CL, 4-coumarate-CoA ligase CTX, cholera toxin FC, fusicoccine GDP-P-S and GTP-y-S, guanosine 5 -0-(2-thiodiphosphate) and guanosine 5 -0-(3-thiotriphosphate) IP3, 1,4,5-inositol trisphosphate PAL, phenylalanine ammonia-lyase PLC, phospholipase C PR, pathogenesis related PTX, pertussis toxin Rc, receptor SP, staurosporine. Activation and inhibition are symbolized by + and -respectively.

This pathway is supported by the demonstration of benzyl alcohol dehydrogenase, benzaldehyde dehydrogenase, benzoyl-CoA ligase, and benzoyl-CoA reductase activities in cell extracts (Biegert and Fuchs 1995). The benzyl alcohol dehydrogenase from benzyl alcohol-grown cells was similar in many of its properties to those from the aerobic bacteria Acinetobacter calcoaceticus and Pseudomonas putida (Biegert et al. 1995). 

Figure 5.4. Abbreviated scheme for biosynthesis of major flavonoid subclasses, showing the primary enzymes and substrates leading to different subclasses. Bold-faced, uppercase abbreviations refer to enzyme names, whereas substrate names are presented in lowercase letters. PAL, phenylalanine ammonia lyase C4H, cinnamate 4-hydroxylase 4CL, 4-coumarate CoA ligase CHS, chalcone synthase CHI, chalcone isomerase CHR, chalcone reductase IPS, isoflavone synthase F3H, flavonone 3-hydroxylase F3 H, flavonoid 3 -hydroxylase F3 5 H, flavonoid 3 5 -hydroxylase FNSI/II, flavone synthase DFR, dihydroflavonol 4-reductase FLS, flavonol synthase ANS, anthocyanidin synthase LAR, leucoanthocyanidin reductase ANR, anthocyanidin reductase UFGT, UDP-glucose flavonoid 3-O-glucosyltransferase. R3 = H or OH. R5 = H or OH. Glc = glucose. Please refer to text for more information.

Figure 6.1 Major branch pathways of flavonoid biosynthesis in Arabidopsis. Branch pathways, enzymes, and end products present in other plants but not Arabidopsis are shown in light gray. Abbreviations cinnamate-4-hydroxylase (C4H), chalcone isomerase (CHI), chalcone synthase (CHS), 4-coumarate CoA-ligase (4CL), dihydroflavonol 4-reductase (DFR), flavanone 3-hydroxylase (F3H), flavonoid 3 or 3 5 hydroxylase (F3 H, F3 5 H), leucoanthocyanidin dioxygenase (LDOX), leucoanthocyanidin reductase (LCR), O-methyltransferase (OMT), phenylalanine ammonia-lyase (PAL), rhamnosyl transferase (RT), and UDP flavonoid glucosyl transferase (UFGT).

CL, 4-coumarate CoA ligase CHS, chalcone synthase CHI, chalcone isomerase F3H, flavanone 3-hydroxylase DFR, dihydroflavonol 4-reductase ANS, anthocyanidin synthase FGT, flavonoid 3-O-glucosyltransferase. 

Structural analysis of several non-NRPS adenyiation domains has provided significant insight into the basis for the multistep chemistry of NRPS A domains. Of note, the X-ray structures of 4-chlorobenzoate-CoA ligase bound to reaction intermediates showed two dramatically different orientations between the large and small domains. The enzyme bound to a substrate analogue was in a similar conformation as the described NRPS A-domain structures. In contrast, the structure of the enzyme bound to a product analogue revealed that... 

The 4-coumarate CoA ligase (4CL EC 6.2.1.12) enzyme activates 4-coumaric acid, caffeic acid, ferrulic acid, and (in some cases) sinapic acid by the formation of CoA esters that serve as branch-point metabolites between the phenylpropanoid pathway and the synthesis of secondary metabolites [46, 47]. The reaction has an absolute requirement for Mg " and ATP as cofactors. Multiple isozymes are present in all plants where it has been studied, some of which have variable substrate specificities consistent with a potential role in controlling accumulation of secondary metabolite end-products. Examination of a navel orange EST database (CitEST) for flavonoid biosynthetic genes resulted in the identification of 10 tentative consensus sequences that potentially represent a multi-enzyme family [29]. Eurther biochemical characterization will be necessary to establish whether these genes have 4CL activity and, if so, whether preferential substrate usage is observed. 

Hamberger B, Hahlbrock K (2004) The 4-coumarate CoA ligase gene family in Arabidopsis thaliana comprises one rare, sinapate-activating and three commonly occurring isoenzymes. Proc Natl Acad Sci USA 101(7) 2209-2214... 

The subsequent cleavage of the thio-ester succinylCoA into succinate and coenzyme A by succinic acid-CoA ligase (succinyl CoA synthetase, succinic thiokinase) is strongly exergonic and is used to synthesize a phosphoric acid anhydride bond ( substrate level phosphorylation , see p. 124). However, it is not ATP that is produced here as is otherwise usually the case, but instead guanosine triphosphate (CTP). However, GTP can be converted into ATP by a nucleoside diphosphate kinase (not shown). 

This enzyme [EC 6.2.1.1], also referred to as acetate-CoA ligase or acetate thiokinase, catalyzes the reaction of acetate, coenzyme A, and ATP to form acetyl-CoA, AMP, and pyrophosphate. The enzyme will also utilize propanoate and propenoate as substrates. 

Succinyl-CoA synthetase (GDP) [EC 6.2.1.4], also known as succinate CoA ligase, catalyzes the reversible reaction of GTP with succinate and coenzyme A to produce GDP, succinyl-CoA, and orthophosphate. The nucleotide substrate can be replaced with ITP and itaconate can substitute for succinate. 

BENZENE 1,2-DIOXYGENASE PHTHALATE DIOXYGENASE BENZOATE-CoA LIGASE BENZOATE 1,2-DI OXYGENASE BENZOYLFORMATE DECARBOXYLASE BERBERINE BRIDGE ENZYME BETA (j8)... 

ARYLAMINE ACETYLTRANSFERASE ATP CITRATE LYASE BENZOATE-CoA LIGASE... 

PROPANEDIOL DEHYDRATASE PROPANEDIOL DEHYDRATASE Propanoyl-CoA, formation of, PROPIONYL-CoA SYNTHETASE Propionate CoA ligase,... 

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