From Ferulic Acid

Ferulic acid is ubiquitously present in plants, mainly as part of the cell walls esterified to polysaccharides such as arabinoxylans. It is also an intermediate in the secondary metabolism of phenylalanine and tyrosine. It can be conveniently isolated from corn hulls, rice bran, and sugar beet. Biocatalytic processes using cinnamoyl esterases and glycosyl hydrolases have been developed for this purpose [32]. Another potentially interesting source is lignin, since ferulic acid is one of the prominent byproducts of its degradation. 

Several microorganisms have been discovered and/or engineered that are able to produce vanillin in high yields from ferulic acid. The most important strains for this purpose are ceitz n y Amycolatopsis sp. in particular, ATCC 39116 (formerly known as Streptomyces setonii) afforded a yield of 13.9 gl [45,46]. 

The introduction of in situ product removal by adsorption on hydrophobic resin greatly improved the yields of some of these processes. For instance, production with Streptomyces sp. V-1 has been increased to 19.5 gl simply by addition of a macroporous adsorbent resin [47], and the production with Amycolatopsis sp. ATCC 39116 has been pushed to 19.5gl in a solid-liquid two-phase partitioning bioreactor [48]. These are the highest values of productivity achieved at present. 

a two-step process was patented in 1996 [49], employing two different filamentous fungi Aspergillus niger and Pycnoporus cinnabarinus. In the first step, A. niger transformed ferulic acid to vanillic acid, and in the second step the latter was reduced to vanillin by P. cinnabarinus [50]. The yields have been improved to over 0.5 gl adding cellobiose to the culture medium [51]. This behavior has been ascribed either to the fact that cellobiose is a more easily metabolized carbon source, required for the reduction to occur, or to its action as an inducer of cellobiose-quinone oxidoreductase, which inhibits vanillic acid decarboxylation. 

This process has been modified to allow the use of a cheap and natural agricultural byproduct (autoclaved maize bran) as a ferulic acid source, with an overall production of 767 mgl in two steps, or 584 mg 1 in one pot (extracellular enzymes of A. niger added to P. cinnabarinus culture) [52]. 

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Attachment of Hydroxycinnamic Acids to Structural Cell Wall Polymers. Peroxidase mediation may also result in binding the hydroxycinnamic acids to the plant cell wall polymers (66,67). For example, it was reported that peroxidases isolated from the cell walls of Pinus elliottii catalyze the formation of alkali-stable linkages between [2-14C] ferulic acid 1 and pine cell walls (66). Presumably this is a consequence of free-radical coupling of the phenoxy radical species (from ferulic acid 1) with other free-radical moieties on the lignin polymer. There is some additional indirect support for this hypothesis, since we have established that E-ferulic acid 1 is a good substrate for horseradish peroxidase with an apparent Km (77 /tM), which is approximately one fifth of that for E-coniferyl alcohol (400 /iM) (unpublished data). 

In 1965, Zenk, using radioactively labelled ferulic and vanillic acids, proposed a route by which both vanillin and vanillic acid were derived from ferulic acid. A CoA-dependent /3-oxidative cleavage of feruloyl-CoA led to the formation of vanilloyl-CoA,... 

Fig. 15.4. The routes (a) from eugenol to ferulic acid and (b) from ferulic acid to vanillin in Pseudomonas strains (Gasson etal., 1998 Mitra etal., 1999).

A scheme for the formation of guaiacols from ferulic acid has also been proposed by Manley et al. (1974). The biosynthesis of various phenolic acids from p-coumaric acid (H.84) was studied by Friedrich (1976). Formation pathways for simple phenols in food flavors have been reviewed (Maga, 1978a). The two primary pathways could be the decarboxylation of phenolic carboxylic acids and the thermal degradation of lignin. Secondary pathways include bacterial, fungal, yeast enzymic and glycosidic reactions. 

Reichstein (1932) prepared it by decarboxylation of ferulic acid (H.87) and by Grignard reaction from vanillin (H.56). It was produced from ferulic acid by yeasts and lactic bacteria (Dubois, 1983). Tressl et al. (1976) and Fiddler et al. (1967) identified it as a thermal decomposition product of ferulic acid. 

Biosynthesis From ferulic acid (see caffeic acid) by chain lengthening with malonyl-CoA and hexanoyl-CoA. Dehydrogingerdione is an intermediate. 

C H, o02, Mr 150.18, bp. 224 °C, mp. 9 -10 C (57 °C). Yellowish oil or crystals with a smell like cloves, olfactory threshold 10 ppb V. forms by fermentation or thermally from ferulic acid and other phenol carboxylic acids and is a constituent of the flavors of beer, bread, coffee, popcorn, wine, tar and smoked food. Lit. Arctander, No. 1891 Biochim. Bittphys. Acta789,111 (1984). Maarse, p. 515. - [CAS 7786-61-0]... 

Graf, N. and Altenbuchner, J. (2014) Genetic engineering of Pseudomonas putida KT2440 for rapid and high-yield production of vanillin from ferulic acid. Appl. Microbiol Biotechnol, 98 (1), 137-149. 

Givaudan developed a strain of Streptomyces, which produces vanillin from ferulic acid. Pseudomonas strains possess this ability too, and fermentation with Amycolatopsis leads similarly to vaniUin. The most important producers of vaniUin from ferulic acid are Symrise and Rhodia (Rhovanil Natural- [152]... 

Treatment of the Methylated Reaction Mixture from -Ferulic Acid 1 with Propane-1,3-dithiol. The crude reaction mixture was methylated as described above. The mixture, 416 mg, was dissolved in 20 mL of anhydrous benzene, and... 

Figure 2 PVG and vanillin formation from ferulic acid following its release...

The poor utilization of ferulic acid raises a point of interest. As mentioned above, there has long been evidence that scopoletin in tobacco arises from ferulic acid. However, this evidently cannot be the case in Agathosma, since scopoletin is well utilized to form puberulin, but ferulic acid is not. It may be that scopoletin, like the other di- and trioxygenated coumarins thus far studied, originates via umbelliferone in most species, and that the picture in tobacco is exceptional. 

MALDI-TOF spectra of several standard phenolic acids were obtained in positive ion linear mode under a Voyager DE Pro (Fig. 66.4). Spectra acquired from ferulic acid showed major ions at m/z 195 corresponding to the protonated [M -i- H]" mass of ferulic acid and with loss of one water molecule [-H2O] show a fragment ion of m/z 177. Direct MALDI-TOF analysis of syringic acid shows major ions at m/z 237 and m/z 221 which might be speculated in the addition of one potassium ion [M + K]" and one sodium ion [M -1- Na]", respectively. MALDI-TOF MS of polyflavons tend to favor an association with sodium [M -1- Na]" and potassium [M I- K] ions over the formation of a protonated molecular ion [M -1- H]" [32]. Another ion was observed at m/z 139 corresponding to the loss of [CO2 -1- CH3] ion. 

Reduction of the benzoic acid carboxyl groups yields the corresponding aldehydes and alcohols, as for instance vanilhn and vanillyl alcohol (XVII and XVIII respectively in Formula 18.18) from 3-methoxy-4-hydroxybenzoic acid and coniferyl alcohol from ferulic acid. 

Other cinnamic acids also produce aldehydes, but they have no significance as odour-active substances. By analogy, coumaralde-hyde is produced from 4-coumaric acid, caffeoyl aldehyde from caffeic acid, conifer aldehyde (also known as ferulyl aldehyde) from ferulic acid, 5-hydroxyconifer aldehyde from 5-hydroxyferulic acid and sinapyl aldehyde from sinapic acid. These aldehydes can be reduced to the corresponding alcohols, with which they play a role as the building units of lignin biosynthesis. 

A group of about 40 amides derived from 5-hydroxyanthranilic or 5-hydroxy-4-methoxyanhranilic acids and cinnamic acids, trivially named avenanthramides, are important phytoalexins unique to oat grains Avena sativa, Poaceae). The dominant compounds are derivatives of 5-hydroxyanthranilic acid avenanthramide Bp derived from p-coumaric acid (also called avenanthramide A, 8-154), avenanthramide Be derived from caffeic acid (also called avenanthramide C) and avenanthramide Bf derived from ferulic acid (also called avenanthramide B). The main compound (40-132 mg/kg) is avenanthramide Bf (8-154). Approximately 6% of oat antioxidants are anthramides derived from caffeic acid. 

Very recently, an alternative strategy has been proposed, which is based on the bioconversion of eugenol to ferulic acid in situ, coupling the advantage of the inexpensiveness of eugenol as substrate with the high yields of vanillin from ferulic acid [53]. 

A. J., Steinbuchel, A., and Priefert, H. (2006) Potential of Rhodococcus strains for biotechnological vanillin production from ferulic acid and eugenol. Appl. Microbiol. Biotechnol, 72, 745—755. 

A two-step bioconversion process for vanillin production from ferulic acid combining Aspergillus niger and Pycno-porus cinnabarinus. J. BiotechrwL, 50, 107-113. 

C., Kim, J., Choi, M., Oh, D., and Kim, S. (2009) Directing vanillin production from ferulic acid by increased acetyl-CoA consumption in recombinant Escherichia coli. Biotechnol. Bioeng,... 

M. (2011) Metabolic engineering of Pseudomonas fluorescens for the production of vanillin from ferulic acid. J, Biotechnol, 156, 309—316. 

First, /7-coumaric acid is subjected to a j8-oxidation which reminds us of the j8-oxidation of the fatty acids and it is possible that the mechanism of the two reactions is the same. At any rate an aromatic acid is produced, the side chain of which is 2 C atoms shorter. It is called /7-hydroxybenzoic acid and is an example of a phenol carboxylic acid. In a completely analogous manner protocatechuic acid is obtained by j8-oxidation of caffeic acid, vanillic acid from ferulic acid, etc. 

The cyclobutane diacid core 5 was assembled from ferulic acid 4 following the procedure of Kibayashi J. Am. Chem. Soc. 2004,126,16553). 

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