Class Course presentation, Department of Biochemistry and Molecular Biology Obafemi Awolowo University, Ile ife Nigeria.

1. BIOSYNTHESIS OF FLAVONOIDS
BCH 614 (Natural Products)
BY
Omotosho Gbemiga O.
SCP17/18/H/1049
and
Oyelekan Esther Ibukunoluwa
SCP18/19/R/0088
Lecturer: Dr. (Akinpelu B.A

2. INTRODUCTION
 Flavonoids are a group of phenolic compounds with 15 carbon
atoms; 2 benzene rings joined by a linear three carbon chain
having a C6-C3-C6 carbon skeleton (Maria et al., 2012).
 They act as antioxidants; and their anti-oxidative property depends
on the molecular structure, presence of conjugated double bonds
and the occurrence of functional groups in the rings.
 Flavonoids are polar and soluble in methanol and water.
 Widely distributed in different amounts, according to the plant
species, organ, developmental stage and growth conditions.

3. Introduction Contd
The antioxidant activities of flavonoids for example,
present in tea, red wine, hops and beer, fruits
vegetable e.t.c.
They have been known to have antiviral, anti-allergic,
anti-inflammatory and antitumor activities etc. They
also provide stress protection.

4. Structure of Flavonoids
 Their basic structure is a skeleton of diphenylpropane, namely, two
benzene rings (ring A and B) linked by a three carbon chain that
forms a closed pyran ring (heterocyclic ring containing oxygen, the
C ring) with benzenic A ring. Therefore, their structure is also
referred to as C6-C3-C6.
 In most cases, B ring is attached to position 2 of C ring, but it can
also bind in position 3 or 4; this, together with the structural features
of the ring B and the patterns of glycosylation and hydroxylation of
the three rings, makes the flavonoids one of the largest and more
diversified groups of phytochemicals.

5. Schematic Diagram
Adapted from Kuhn et al. (2011).

6. BIOSYNTHESIS OF FLAVONOIDS
• The biosynthesis of flavonoids start with the
condensation of one P-coumaroylCoA molecule
(shikimate derived, B ring) with three molecules of
malonyl-CoA (polyketid origin, A ring) to give
chalcone (2′, 4′, 6′, 4-tetrahydroxychalcone) catalized
by chalcone synthase (CHS) enzyme.
• Chalcone is subsequently isomerized by the enzyme
chalcone flavanone isomerase (CHI) to flavanone
• From these central intermediates, the pathway
diverges into several side branches, each yielding a
different class of flavonoids

7. PAL: Phenylalanine lyase
C4H: Cinnamate 4 hydroxylase
4CL: 4-Coumaryl lyase
CHS: Chalcone synthase
CHI: Chalcone isomerase
DFR: Dihydroxyflavanone reductase
ANS: Anthocyanidin synthase
IFS: Isoflavonone synthase
3GT: 3-O glucosyltransferase
FSI: Flavone synthase
FHT: Flavanone 3b hydroxylase
FLS: Flavonol synthase
Phenylalanine Cinnamic acid
Caffeic acid
Malonyl CoA
Isoflavones
Flavan-4-ols
IFSDFR
FSI3GT
CHI
CHS
PAL
4CL
Acid CoA Complex
BIOSYNTHESIS OF FLAVONOIDS
Adapted from Maria et al. (2012).

9. The B ring formation is produced by a Shikimate pathway

10. Formation of A-Ring via Acetate pathway
(Figure 2)

11. Simplified biosynthesis of Flavonoids
pathway
Phenylalanin
PAL
Figure 5

12. Biosynthesis of flavonoids continue
Abbreviations of Enzymes
ACTs = Acetyl transferases
ANR = Anthocyanidin reductase;
ANS = Anthocyanidin synthase (also
known as leucoanthocyanidin
dioxygenase LDOX)
C4H = Cinnamate-4-hydroxylase
CHI = Chalcone isomerase
CHR = Chalcone reductase
CHS = Chalcone synthase
4CL = 4-coumaroyl:CoA-ligase
DFR = Dihydroflavonol 4-reductase
DMID = 7,2'-dihydroxy, 4‘-
methoxyisoflavanol dehydratase
F3H = Flavanone 3-hydroxylase
FNSI and FNSII, flavone synthase I
and II
F3’H and F3’5’H = Flavonoid 3’ and
3’5’ hydroxylase
IOMT = Isoflavone O-
methyltransferase
IFR = Isoflavone reductase
I2’H = Isoflavone 2'-hydroxylase
IFS = Isoflavone synthase
LAR = Leucoanthocyanidin reductase
OMTs= O-methyltransferase
PAL = Phenylalanine ammonia-lyase
GTs = Glucosyl transferases
VR = Vestitone reductase.

13. REGULATORY MECHANISM
 The synthesis of flavonoids begins from phenylalanine in the shikimate pathway,
converting phenylalanine into 4-coumaroyl- CoA, which then enters the flavonoid
biosynthesis pathway through chalcone intermediate (Maria et al., 2012).
 Regulatory enzyme specific for flavonoid pathway includes Phenylalanin Ammonia
Lyase (PAL), Chalcone synthase (CHS), the enzyme produces Chalcone scaffolds from
which all flavonoids derive, also Flavone 3-Hydroxylase (F3-H), which regulate the
biosynthesis of Leucocyanidine in addition to these regulatory enzymes are
Anthocyanidine synthase (ANS) (also known as Leucothocyanidin dioxygenase
(LDOX)) that regulate the biosynthesis of Anthocyanidins and Glutathion S-Transferase
(GST) that regulate the biosynthesis of Anthocyanins.

14. Scheme presentation of Regulation of
Anthocyanins (Flavonoid) biosynthesis
Figure : 6

15. Schematic presentation of Gene Regulation of
Anthocyanin biosynthesis (A Flavonoid)
Figure: 7

16. Conclusion
 Flavonoids are found in most plant tissues – where they provide
brilliant colors that attract pollinators. The pigments act as
antioxidants and sunscreens, absorbing UV radiation.
 Their biosynthesis appears to be ubiquitous in plants and evolved
early in life, providing protection and signaling in plants .
 The regulatory mechanism is both genetic and subcellular
localization of flavonoid pathways with Chalcone synthase being the
first regulatory enzyme specific for flavonoid biosynthesis.

17. References
Dixon, R.A.; Pasinetti, G.M. (2010). Flavonoids and isoflavonoids: from plant
biology to agriculture and neuroscience. Plant Physiology, 154: 453-457.
Iwashina, T. (2000). The structure and distribution of the flavonoids in plants.
Journal of Plant Research, 113: 287-299.
Kuhn, B.M. ,Geisler,M.,Bigler,L.,and Ringli,C.(2011).Flavonols accu mulate
asymmetrically and affect auxin transportin Arabidopsis. PlantPhysiol. 156| 585–595.
María, L. F. F., Sebastián, P. R. and Paula, C. (2012). Flavonoids: biosynthesis,
biological functions,and biotechnological applications. Frontiers in plant science. 3(222):1-
15.
Martens, S., Preuss, A., and Matern, U. (2010). Multifunctional flavonoid
dioxygenases: flavonols and antho-cyaninbiosynthesis in Arabidopsis thaliana L.
Phytochemistry, 71: 1040–1049.
Owens, D.K., Alerding, A.B., Crosby, K.C., Bandara, A.B., Westwood, J.H., and
Winkel, B.S.J.(2008). Functional analysis of a predicted flavonol synthase gene family in
Arabidopsis. Plant Physiol. 147: 1046–1061.

18. References contd.
Martens S, Preuss A, Matern U. Multifunctional flavonoid
dioxygenases: flavonols and anthocyanin biosynthesis in Arabidopsis thaliana
L. Phytochemistry. 2010;71:1040-1049.
Markham K.R. Distribution of flavonoids in the lower plants and its
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research since 1980 (1st ed.). London: Chapman & Hall; 1988, pp. 427-464.
Markham K.R, Porter L.J. Flavonoids in the green algae
(chlorophyta). Phytochemistry. 1969;8:1777-1781.
Oh H, Kim DH, Cho JH, Kim YC. Hepatoprotective and free radical
scavenging activities of phenolic petrosins, flavonoids isolated from Equisetum
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Vassao D, Kim KW, Davin LB, Lewis NG. Lignans (neolignans) and
allyl/propenyl phenols: biogenesis, structural biology, and biological/human
health considerations. In: Mander L, Liu H-WB, editors. Comprehensive
natural products II (1st ed.). Oxford: Elsevier; 2010, pp. 815-928.

19. • Thank
you
for
listening