PHENOLIC COMPOUNDS

Phenolic compounds constitute a diverse group of natural organic compounds identifiable by

the presence of a phenol ring, a six-membered carbon ring containing an oxygen atom. These
compounds serve essential roles in plants, acting as secondary metabolites that contribute to plant
defense mechanisms against environmental stressors, pathogens, and UV radiation.

Phenolic compounds are widely distributed in the plant kingdom, with high concentrations
found in fruits, vegetables, whole grains, tea, coffee, and various nuts. This class of compounds is
remarkably varied, encompassing flavonoids, phenolic acids, lignans, and other subclasses, each
exhibiting distinct biological activities and health-promoting properties. Notably, phenolic compounds
are recognized for their antioxidant properties, which may help counteract oxidative stress and reduce
the risk of chronic diseases in humans.

Consuming foods rich in phenolic compounds is linked to potential health benefits, including
anti-inflammatory, anti-cancer, and cardiovascular protective effects. A comprehensive understanding
of the sources and biological activities of phenolic compounds sheds light on their significance for
human health, emphasizing the importance of incorporating a diverse array of plant-based foods into
one's diet.

SHIKIMATE PATHWAY

The shikimate pathway plays a pivotal role in synthesizing fundamental building blocks for a
diverse array of aromatic metabolites and aromatic amino acids. These metabolites derived from
aromatic compounds serve multiple essential functions, including providing ultraviolet protection,
acting as electron transport carriers, functioning as signaling molecules, and serving as antibacterial
agents.

The shikimic acid pathway begins with the reaction of phosphoenolpyruvate and erythrose-4-
phosphate, ultimately leading to the formation of 3-dehydroquinate through a series of steps. Shikimate
dehydrogenase catalyzes the dehydration of 3-dehydroquinate, yielding 3-dehydroshikimic acid.
Reduction of 3-dehydroshikimic acid with NADPH results in the formation of shikimic acid. Further
transformations of 3-dehydroshikimic acid can lead to the production of gallic acid through several
enzymatic steps.

Shikimic acid undergoes subsequent conversions, with chorismic acid being a key
intermediate. The enzyme chorismate synthase, activated by the reduced cofactor flavin
mononucleotide, facilitates the conversion of chorismic acid. Following a Claisen rearrangement,
prephenic acid is produced, and through additional steps, it is ultimately transformed into tyrosine.
Tyrosine, as a central amino acid in this pathway, serves as a crucial precursor for the biosynthesis of
various phenolic compounds, highlighting the importance of the shikimate pathway in the synthesis of
biologically significant molecules with diverse functions.

Fig. 1 Shikimate Pathway

SHIKIMIC ACID PATHWAY TOWARD PHENOLIC COMPOUNDS

The biosynthesis of coumarins in plants initiates within the phenylpropanoid pathway, a

sequence that begins with the utilization of phenylalanine as the primary substrate. The pathway
involves the ortho-hydroxylation of cinnamates, specifically trans-cinnamic acid, p-coumaric acid,
caffeic acid, and ferulic acid. This series of transformations leads to the formation of various coumarin
derivatives, including coumarin itself, along with umbelliferone, esculetin, scopoletin, and fraxetin.

The phenylpropanoid pathway shares a foundational similarity with the shikimic acid pathway
up to the L-phenylalanine stage, where it diverges to take on its distinct form. At this point, L-
phenylalanine undergoes deamination catalyzed by the enzyme phenylalanine ammonia lyase (PAL),
resulting in the production of cinnamic acid. Through subsequent hydroxylation and conversion to
Coenzyme A, p-coumaroyl Coenzyme A is generated. This pivotal molecule serves as a central point
from which various phenolic compounds, including coumarins, can be synthesized, underscoring the
significance of the phenylpropanoid pathway in the production of diverse and biologically relevant
plant metabolites.

Fig. 2. Phenylpropanoid pathway

 Flavonoids, a diverse class of plant secondary metabolites with various biological activities,
are synthesized through the phenylpropanoid pathway. This pathway begins with the conversion of
phenylalanine into 4-coumaroyl-CoA. Once synthesized, 4-coumaroyl-CoA enters the flavonoid
biosynthesis pathway, where a series of enzymatic reactions give rise to the formation of flavonoids.

A key enzyme in the flavonoid pathway is chalcone synthase, which catalyzes the production
of chalcone scaffolds. Chalcones serve as essential precursors and central intermediates from which all
flavonoids ultimately derive. The subsequent modification and diversification of chalcone structures
through various enzymatic steps contribute to the vast array of flavonoids found in plants. This intricate
process within the phenylpropanoid pathway and the specific role of chalcone synthase highlight the
complexity and versatility of flavonoid biosynthesis in plants.

Fig. 3. Flavonoid pathway in plants

Genes encoding enzymes for each step are indicated as follows: PAL, phenylalanine ammonia-lyase;
C4H, cinnamate 4-hydroxylase; 4CL, 4-coumarate-CoA ligase; CHS, chalcone synthase; CHI,
chalcone isomerase; F3H, flavanone 3-hydroxylase; DFR, dihydroflavonol 4-reductase; LDOX,
leucoanthocyanidin dioxygenase; FLS, flavonol synthase; LAR, leucoanthocyanidin reductase; ANR,
anthocyanidin reductase; UFGT, UDP-glucose:flavonoid-3-O-glycosyltransferase.

Tannins are divided into two major classes: condensed tannins or proanthocyanidins and
hydrolysable tannins. Hydrolysable tannin synthesis branches directly from the shikimate pathway,
while condensed tannins are derived from the flavonoid pathway, one of the branches of the
phenylpropanoid pathway.
 The activation of phenolic compound production in plants involves intricate regulatory
mechanisms that are generally triggered in response to environmental stress. When plants encounter
stressors such as pathogens, UV radiation, herbivore attacks, or physical damage, specialized receptor
proteins on the cell membrane perceive specific signals associated with these challenges. Subsequently,
intracellular signaling pathways are activated, often involving second messengers like calcium ions or
reactive oxygen species. These pathways lead to alterations in gene expression, particularly in genes
related to the phenylpropanoid pathway, a key biosynthetic route for phenolic compounds.
Transcription factors and regulatory proteins modulate the expression of these genes, initiating the
activation of enzymes such as phenylalanine ammonia-lyase (PAL), which converts phenylalanine into
cinnamic acid. Through a series of enzymatic reactions, cinnamic acid is then transformed into various
phenolic compounds, including flavonoids, lignins, and phenolic acids. The newly synthesized
phenolic compounds accumulate within plant tissues, where they serve as vital components of the
plant's defense arsenal, reinforcing its resilience and contributing to its adaptive response to
environmental challenges.

References

Ferreyra, M.L., Ruis, S.P & Casati, P. (2012). Flavonoids: Biosynthesis, biological functions, and
biotechnological applications. 10.3389/fpls.2012.00222
Ravagilla, D., Espley, R., Henry-Kirk, R.A., & Andreotti, C. (2013) Transcriptional regulation of
flavonoid biosynthesis in nectarine (Prunus persica) by a set of R2R3 MYB transcription
factors. 10.1186/1471-2229-13-68
Mamari, H.H (2021, June 10). Phenolic Compounds: Classification, Chemistry, and Updated
Techniques of Analysis and Synthesis. DOI: 10.5772/intechopen.98958

Yifan, S., Guangxi, R., Qijin S., Hongyu Z., Na, Z., Xianghe, K., Dan, J., & Chunsheng, L. (2023,
January 4) Identification of a Novel Coumarins Biosynthetic Pathway in the Endophytic
Fungus Fusarium oxysporum GU-7 with Antioxidant Activity.
https://doi.org/10.1128/aem.01601-22