Cinnamoyl CoA

Ralph, J. Kim, H. Lu, F. Grabber, J. H. Boerjan, W. Leple, J.-C. Berrio Sierra, J. Mir Derikvand, M. Jouanin, L. Lapierre, C. Identification of the structure and origin of a thioacidolysis marker compound for ferulic acid incorporation into angiosperm lignins (and an indicator for cinnamoyl-CoA reductase deficiency). Plant J. 2008, 53, 368-379. 

Members of the CHS/STS family of condensing enzymes are relatively modest-sized proteins of 40-47 kDa that function as homodimers. Each enzyme typically reacts with a cinnamoyl-CoA starter unit and catalyzes three successive chain extensions with reactive acetyl groups derived from enzyme catalyzed decarboxylation of malonyl-CoA.11 Release of the resultant tetraketide together with or prior to polyketide chain cyclization and/or decarboxylation yields chalcone or resveratrol (a stilbene). Notably, CHS and STS catalyze identical reactions up to the formation of the intermediate tetraketide. Divergence occurs during the termination step of the biosynthetic cascade as each tetraketide intermediate undergoes a distinct cyclization reaction (Fig. 12.2). 

The first STS structure solved was that of a pinosylvin-forming STS from Pinus sylvestris. Pine trees can by-pass the C4H reaction and directly produce the CoA thioester of cinnamate that allows this STS to utilize a non-substituted cinnamoyl-CoA starter in vz vo.11 However, when presented in vitro with p-coumaroyl-CoA, the enzyme proves to be comparable in activity to STS enzymes from organisms that utilize the para-substituted cinnamoyl starter. 

ABE, I., MORITA, H NOMURA, A., NOGUCHI, H., Substrate specificity of chalcone synthase enzymatic formation of unnatural polyketides from synthetic cinnamoyl-CoA analogues, J. Am. Chem. Soc., 2000,122,11242-11243. 

This enzyme [EC 6.2.1.12] (also referred to as hydroxy-cinnamoyl-CoA ligase and 4-coumarate CoA hgase) catalyzes the reaction of 4-coumarate with ATP and coenzyme A to yield 4-coumaroyl-CoA, AMP, and pyrophosphate (or, diphosphate). 

CHS carries out a series of sequential decarboxylation and condensation reactions, using 4-courmaroyl-CoA (in most species) and three molecules of malonyl-CoA, to produce a poly-ketide intermediate that then undergoes cyclization and aromatization reactions that form the A-ring and the resultant chalcone structure. The chalcone formed from 4-courmaroyl-CoA is naringenin chalcone. However, enzyme preparations and recombinant CHS proteins from some species have been shown to accept other HCA-CoA esters as substrates, such as cinnamoyl-CoA (see, e.g., Ref. 37). In particular, the Hordeum vulgare (barley) CHS2 cDNA encodes a CHS protein that converts feruloyl-CoA and caffeoyl-CoA at the highest rate, and cinnamoyl-CoA and 4-courmaroyl-CoA at lower rates. 

Morus alba callus and cell suspension cultures specifically produce chalomoradn 5 and kuwanon J 6 from dnnamoylpolyketide intermediates. Administration of [2- C]cinnamic add AT-acetylcysteamine thioester to the M. alba cell cultures revealed the cinnamoyl CoA intermediate to be a significant precursor <99H(50)989>. For further biosynthetic investip-tions see <99H(51)231>. 

Cilia 10,15. See also flagella eukaryotic structure 15 Ciliophora 19 Cinnamic acid 756s Cinnamoyl-CoA thiol esters 682 Circular dichroism (CD)... 

Most of the pigments of flowers arise from a single polyketide precursor. Phenylalanine is converted to trans-cinnamic acid (Eq. 14-45) and then to cinnamoyl-CoA. The latter acts as the starter piece for chain elongation via malonyl-CoA (step a in the accompanying scheme). The resulting (3-polyketone derivative can cyclize in two ways. The aldol condensation (step b) leads to stilbenecar-boxylic acid and to such compounds as pinosylvin of pine trees. The Claisen condensation (step c) produces chalcones, flavonones, and flavones. These, in turn, can be converted to the yellow fla-vonol pigments and to the red, purple, and blue anthocyanidins.3 c... 

The reduction of />coumaroyl-CoA (3.31) to />coumaryl aldehyde (3.69) is catalyzed by the enzyme cinnamoyl-CoA NADP oxidoreductase (CCR). This enzyme was initially purified from soybean cultures (Wegenmayer et al., 1976), and was later on efficiently isolated from lignifying cambium of eucalyps (Eucalyptus gunnii) (Gofifiier et al., 1994). A CCR cDNA was identified in a cDNA library that was screened with oligonucleotiede derived from the peptide sequence of the CCR protein. CCR is considered the first enzyme committed towards the biosynthesis of monolignols and shows... 

Figure 3-9. Biosynthesis of monolignols. The enzymes involved in this pathway are ( ) hydroxycinnamoyl-CoA shikimate/quinate hydroxy-cinnamoyl transferase, (b) p-coumaroyl-CoA 3 -hydroxylase (E.C. 1.14.14.1), (c) caffeoyl-CoA O-methy 1 Iranslerasc (E.C. 2.1.1.104), (d) cinnamoyl-CoA reductase (E.C. 1.2.1.44) (e) cinnamyl alcohol dehydrogenase (E.C. 1.1.1.195), (f) coniferyl aldehyde/coniferyl alcohol 5-hydroxylase (E.C. 1.14.13), (g) coniferaldehyde/coniferyl alcohol O-methyltransferase (E.C. 2.1.1.68).

Goffner, D., Campbell, M.M., Campargue, C., Clastre, M., Borderies, G., Boudet, A. and Boudet, A.M., 1994, Purification and characterization of cinnamoyl-CoA NADP oxidoreductase in Eucalyptus gunnii, Plant Physiol. 106 625-632. 

Wegenmayer, H., Ebel, J. and Grisebach, H., 1976, Enzymic synthesis of lignin precursors Purification and properties of a cinnamoyl-CoA NADPH reductase from cell suspension cultures of soybean (Glycine max L.), Eur. J. Biochem. 65 529-536. 

O Connell, A., Holt, K., Piquemal, J., Grima-Pettenati, J., Boudet, A., Pollet, B., Lapierre, C., Petit-Conil, M., Schuch, W., and Halpin, C. 2002, Improved paper pulp from plants with suppressed cinnamoyl-CoA reductase or cinnamyl alcohol dehydrogenase, Transgen. Res. 11 495-503. 

Lauvergeat, V., Lacomme, C., Lacombe, E., Lasserre, E., Roby, D., and Grima-Pettenati, J., 2001, Two cinnamoyl-CoA reductase (CCR) genes from Arabidopsis thaliana are differentially expressed during development and in response to infection with pathogenic bacteria, Phytochem. 57 1187-1195. 

Pichon, L. Courbou, I, Beckert, M, Boudet, A-M., and Grima-Pettenati, J., 1998, Cloning and characterization of two maize cDNAs encoding cinnamoyl-CoA reductase (CCR) and differential expression of the corresponding genes, Plant Mol. Biol. 38 671-676. 

Flavonoids and stilbenes are simple examples of molecules in which a suitable cinnamoyl-CoA C6C3 precursor from the shikimate pathway (see... 

The polyketide synthases responsible for chain extension of cinnamoyl-CoA starter units leading to flavonoids and stilbenes, and of anthraniloyl-CoA leading to quinoline and acridine alkaloids (see page 377) do not fall into either of the above categories and have now been termed Type TTT PKSs. These enzymes differ from the other examples in that they are homodimeric proteins, they utilize coenzyme A esters rather than acyl carrier proteins, and they employ a single active site to perform a series of decarboxylation, condensation, cyclization, and aromatization reactions. 

Cinnamic acids, as their coenzyme A esters, may also function as starter units for chain extension with malonyl-CoA units, thus combining elements of the shikimate and acetate pathways (see page 80). Most commonly, three C2 units are added via malonate giving rise to flavonoids and stilbenes, as described in the next section (page 149). However, there are several examples of products formed from a cinnamoyl-CoA starter... 

Both structures nicely illustrate the different characteristic oxygenation patterns in aromatic rings derived from the acetate or shikimate pathways. With the stilbenes, it is noted that the terminal ester function is no longer present, and therefore hydrolysis and decarboxylation have also taken place during this transformation. No intermediates, e.g. carboxylated stilbenes, have been detected, and the transformation from cinnamoyl-CoA/malonyl-CoA to stilbene is catalysed by the single enzyme. Resveratrol has assumed greater relevance in recent years as a constituent of grapes and wine, as well as other food products, with antioxidant, anti-inflammatory, anti-platelet, and cancer preventative properties. Coupled with... 

The piperic acid portion is derived from a cinnamoyl-CoA precursor, with chain extension using acetate/malonate (compare flavonoids, page 149), and combines as its CoA ester with piperidine. 

Maria, C.R. del, Barbara, N.T. and David, R.G. (2006) Biosynthesis of curcuminoids and gingerols in turmeric (Curcuma longa) and ginger (Zingiber officinale) identification of curcuminoid synthase and hydroxy-cinnamoyl-CoA thioesterases. Phytochemistry 67, 201 7-2029. 

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