Phenylpropanoids metabolism

Last updated June 07, 2021

The biosynthesis of phenylpropanoids involves a number of enzymes.

From amino acids to cinnamates

In plants, all phenylpropanoids are derived from the amino acids phenylalanine and tyrosine.

Phenylalanine ammonia-lyase (PAL, a.k.a. phenylalanine/tyrosine ammonia-lyase) is an enzyme that transforms L-phenylalanine and tyrosine into trans-cinnamic acid and p-coumaric acid, respectively.

Trans-cinnamate 4-monooxygenase (cinnamate 4-hydroxylase) is the enzyme that transforms trans-cinnamate into 4-hydroxycinnamate (p-coumaric acid). 4-Coumarate-CoA ligase is the enzyme that transforms 4-coumarate (p-coumaric acid) into 4-coumaroyl-CoA.^[1]

Enzymes associated with biosynthesis of hydroxycinnamic acids

Cinnamyl-alcohol dehydrogenase (CAD), an enzyme that transforms cinnamyl alcohol into cinnamaldehyde
Sinapine esterase, an enzyme that transforms sinapoylcholine into sinapate (sinapic acid) and choline
Trans-cinnamate 2-monooxygenase, an enzyme that transforms trans-cinnamate (cinnamic acid) into 2-hydroxycinnamate
Caffeate O-methyltransferase, an enzyme that transforms caffeic acid into ferulic acid
Caffeoyl-CoA O-methyltransferase, an enzyme that transforms caffeoyl-CoA into feruloyl-CoA
5-O-(4-coumaroyl)-D-quinate 3'-monooxygenase, an enzyme that transforms trans-5-O-(4-coumaroyl)-D-quinate into trans-5-O-caffeoyl-D-quinate
Sinapoylglucose—choline O-sinapoyltransferase, an enzyme that transforms 1-O-sinapoyl-beta-D-glucose into sinapoylcholine (sinapine)
Sinapoylglucose—malate O-sinapoyltransferase, an enzyme that transforms 1-O-sinapoyl-beta-D-glucose into sinapoyl-(S)-malate
Cinnamoyl-CoA reductase, an enzyme that transforms cinnamoyl-CoA from cinnamaldehyde

Conjugation enzymes

These enzymes conjugate phenylpropanoids to other molecules.

2-coumarate O-beta-glucosyltransferase, the enzyme that transforms trans-2-hydroxycinnamate into trans-beta-D-glucosyl-2-hydroxycinnamate
Hydroxycinnamate 4-beta-glucosyltransferase, the enzyme that transforms p-coumaric acid into 4-O-beta-D-glucosyl-4-hydroxycinnamate
Shikimate O-hydroxycinnamoyltransferase, the enzyme that transforms 4-coumaroyl-CoA into 4-coumaroylshikimate
Quinate O-hydroxycinnamoyltransferase, the enzyme that transforms feruloyl-CoA into O-feruloylquinate
Sinapate 1-glucosyltransferase, the enzyme that transforms sinapate (sinapic acid) into 1-sinapoyl-D-glucose
Coniferyl-alcohol glucosyltransferase, the enzyme that transforms coniferyl alcohol into coniferin

Glucosidases

Coniferin beta-glucosidase, the enzyme that transforms coniferin into coniferol

Stilbenoids biosynthesis

Pinosylvin synthase, an enzyme that transforms pinosylvin from cinnamoyl-CoA
Trihydroxystilbene synthase, an enzyme that transforms 4-coumaroyl-CoA to resveratrol.

An alternative bacterial ketosynthase-directed stilbenoids biosynthesis pathway exists in Photorhabdus bacterial symbionts of Heterorhabditis nematodes, producing 3,5-dihydroxy-4-isopropyl-trans-stilbene for antibiotic purposes.^[2]

Coumarins biosynthesis

Scopoletin glucosyltransferase, the enzyme that transforms scopoletin into scopolin

Chalcones biosynthesis

4-Coumaroyl-CoA can be combined with malonyl-CoA to yield the true backbone of flavonoids, a group of compounds called chalconoids, which contain two phenyl rings. Naringenin-chalcone synthase is an enzyme that catalyzes the following conversion:

3-malonyl-CoA + 4-coumaroyl-CoA → 4 CoA + naringenin chalcone + 3 CO₂

Flavonoids biosynthesis

Conjugate ring-closure of chalcones results in the familiar form of flavonoids, the three-ringed structure of a flavone.

Biodegradation

Hydroxycinnamic acids degradation

Caffeate 3,4-dioxygenase is an enzyme that uses 3,4-dihydroxy-trans-cinnamate (caffeic acid) and oxygen to produce 3-(2-carboxyethenyl)-cis,cis-muconate.

Related Research Articles

Silibinin (INN), also known as silybin (both from Silybum, the generic name of the plant from which it is extracted), is the major active constituent of silymarin, a standardized extract of the milk thistle seeds, containing a mixture of flavonolignans consisting of silibinin, isosilibinin, silychristin, silidianin, and others. Silibinin itself is a mixture of two diastereomers, silybin A and silybin B, in approximately equimolar ratio. The mixture exhibits a number of pharmacological effects, particularly in the fatty liver, non-alcoholic fatty liver, non-alcoholic steatohepatitis, and there is great clinical evidence for the use of silibinin as a supportive element in alcoholic and Child–Pugh grade 'A' liver cirrhosis. However, despite its several beneficial effects on the liver, silibinin and all the other compounds found in silymarin, especially silychristin seem to act as potent disruptors of the thyroid system by blocking the MCT8 transporter. The long term intake of silymarin can lead to some form of thyroid disease and if taken during pregnancy, silymarin can cause the development of the Allan–Herndon–Dudley syndrome. Although this information is unfortunately still not being taken into consideration by all regulatory bodies, several studies now consider silymarin and especially silychristin to be important inhibitors of the MCT8 transporter and a potential disruptor of the thyroid hormone functions.

Shikimic acid, more commonly known as its anionic form shikimate, is a cyclohexene, a cyclitol and a cyclohexanecarboxylic acid. It is an important biochemical metabolite in plants and microorganisms. Its name comes from the Japanese flower shikimi, from which it was first isolated in 1885 by Johan Fredrik Eykman. The elucidation of its structure was made nearly 50 years later.

Rutin, also called rutoside, quercetin-3-O-rutinoside and sophorin, is the glycoside combining the flavonol quercetin and the disaccharide rutinose. It is a citrus flavonoid found in a wide variety of plants including citrus.

Hesperidin is a flavanone glycoside found in citrus fruits. Its aglycone form is called hesperetin. Its name is derived from the word "hesperidium", for fruit produced by citrus trees.

Apigenin (4′,5,7-trihydroxyflavone), found in many plants, is a natural product belonging to the flavone class that is the aglycone of several naturally occurring glycosides. It is a yellow crystalline solid that has been used to dye wool.

Kaempferol (3,4′,5,7-tetrahydroxyflavone) is a natural flavonol, a type of flavonoid, found in a variety of plants and plant-derived foods including kale, beans, tea, spinach and broccoli. Kaempferol is a yellow crystalline solid with a melting point of 276–278 °C (529–532 °F). It is slightly soluble in water and highly soluble in hot ethanol, ethers, and DMSO. Kaempferol is named for 17th-century German naturalist Engelbert Kaempfer.

p-Coumaric acid is a hydroxycinnamic acid, an organic compound that is a hydroxy derivative of cinnamic acid. There are three isomers of coumaric acid—o-coumaric acid, m-coumaric acid, and p-coumaric acid—that differ by the position of the hydroxy substitution of the phenyl group. p-Coumaric acid is the most abundant isomer of the three in nature. p-Coumaric acid exists in two forms trans-p-coumaric acid and cis-p-coumaric acid.

The phenylpropanoids are a diverse family of organic compounds that are synthesized by plants from the amino acids phenylalanine and tyrosine. Their name is derived from the six-carbon, aromatic phenyl group and the three-carbon propene tail of coumaric acid, which is the central intermediate in phenylpropanoid biosynthesis. From 4-coumaroyl-CoA emanates the biosynthesis of myriad natural products including lignols, flavonoids, isoflavonoids, coumarins, aurones, stilbenes, catechin, and phenylpropanoids. The coumaroyl component is produced from cinnamic acid.

Daidzein is a naturally occurring compound found exclusively in soybeans and other legumes and structurally belongs to a class of compounds known as isoflavones. Daidzein and other isoflavones are produced in plants through the phenylpropanoid pathway of secondary metabolism and are used as signal carriers, and defense responses to pathogenic attacks. In humans, recent research has shown the viability of using daidzein in medicine for menopausal relief, osteoporosis, blood cholesterol, and lowering the risk of some hormone-related cancers, and heart disease.

Rosmarinic acid is a chemical compound found in a variety of plants. It was found to exhibit photoprotective effect against ultraviolet C (UVC) damage when examined in vitro.

Chalcone synthase or naringenin-chalcone synthase (CHS) is an enzyme ubiquitous to higher plants and belongs to a family of polyketide synthase enzymes (PKS) known as type III PKS. Type III PKSs are associated with the production of chalcones, a class of organic compounds found mainly in plants as natural defense mechanisms and as synthetic intermediates. CHS was the first type III PKS to be discovered. It is the first committed enzyme in flavonoid biosynthesis. The enzyme catalyzes the conversion of 4-coumaroyl-CoA and malonyl-CoA to naringenin chalcone.

In enzymology, a 5-O-(4-coumaroyl)-D-quinate 3'-monooxygenase (EC 1.14.13.36) is an enzyme that catalyzes the chemical reaction

In enzymology, a trans-cinnamate 4-monooxygenase (EC 1.14.14.91) is an enzyme that catalyzes the chemical reaction

Flavonoids are synthesized by the phenylpropanoid metabolic pathway in which the amino acid phenylalanine is used to produce 4-coumaroyl-CoA. This can be combined with malonyl-CoA to yield the true backbone of flavonoids, a group of compounds called chalcones, which contain two phenyl rings. Conjugate ring-closure of chalcones results in the familiar form of flavonoids, the three-ringed structure of a flavone. The metabolic pathway continues through a series of enzymatic modifications to yield flavanones → dihydroflavonols → anthocyanins. Along this pathway, many products can be formed, including the flavonols, flavan-3-ols, proanthocyanidins (tannins) and a host of other various polyphenolics.

In enzymology, a 4-coumarate-CoA ligase is an enzyme that catalyzes the chemical reaction

In enzymology, a sinapoylglucose---choline O-sinapoyltransferase is an enzyme that catalyzes the chemical reaction

In enzymology, a 2-coumarate O-beta-glucosyltransferase is an enzyme that catalyzes the chemical reaction

Naringenin chalcone is a common chalconoid. It is synthesized from 4-coumaroyl-CoA and malonyl-CoA by chalcone synthase (CHS), a key enzyme in the phenylpropanoid pathway. Naringenin chalcone can spontaneously cyclize to naringenin. In plant cells, this process is catalyzed by chalcone isomerase.

Coumaroyl-coenzyme A is a chemical compound found in plants. The compound is the thioester of coenzyme-A and coumaric acid.

Umbellic acid is a hydroxycinnamic acid. It is an isomer of caffeic acid.

References

↑ Ververidis Filippos, F.; Trantas Emmanouil; Douglas Carl; Vollmer Guenter; Kretzschmar Georg; Panopoulos Nickolas (October 2007). "Biotechnology of flavonoids and other phenylpropanoid-derived natural products. Part I: Chemical diversity, impacts on plant biology and human health". Biotechnology Journal. 2 (10): 1214–34. doi:10.1002/biot.200700084. PMID 17935117.
↑ Joyce SA, Brachmann AO, Glazer I, Lango L, Schwär G, Clarke DJ, Bode HB (2008). "Bacterial biosynthesis of a multipotent stilbene". Angew Chem Int Ed Engl. 47 (10): 1942–5. CiteSeerX 10.1.1.603.247 . doi:10.1002/anie.200705148. PMID 18236486.

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[1] Ververidis Filippos, F.; Trantas Emmanouil; Douglas Carl; Vollmer Guenter; Kretzschmar Georg; Panopoulos Nickolas (October 2007). "Biotechnology of flavonoids and other phenylpropanoid-derived natural products. Part I: Chemical diversity, impacts on plant biology and human health". Biotechnology Journal. 2 (10): 1214–34. doi:10.1002/biot.200700084. PMID 17935117.

[2] Joyce SA, Brachmann AO, Glazer I, Lango L, Schwär G, Clarke DJ, Bode HB (2008). "Bacterial biosynthesis of a multipotent stilbene". Angew Chem Int Ed Engl. 47 (10): 1942–5. CiteSeerX 10.1.1.603.247 . doi:10.1002/anie.200705148. PMID 18236486.

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