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123
Transcriptional Regulation in Biosynthesis
of Phytochemicals in Medicinal Plants
Under Stress Conditions
8
Akruti Gupta, Kishore Kumar Gupta, Sanjay Kumar Gupta,
and Prashant Kumar Mishra
Abstract
Mitigation to stress conditions in plants is critically favoured by the increased
synthesis of specialized bioactive metabolites known as the “secondary
metabolites (SMs).” The elicitation that brings about this change is initiated at
the level of the shikimate pathway that produces aromatic amino acids as the
ultimate precursors of the SMs. These precursor molecules enhance the biosyn-
thesis of the SMs in response to the abiotic stresses by stimulating their condi-
tional accumulation in different plant parts. On the other hand, the response to
biotic stresses is controlled by biotic or abiotic elicitors that specifically induce
the synthesis of specific compounds enabling the adaptation to stressful
conditions. Overall, the modulation in secondary metabolism is mediated by a
variety of transcriptional factors (TFs), such as WRKY, MYB, AP2/ERF, bZIP,
bHLH and NAC. The TFs regulate the genes associated with biosynthetic
pathways of the metabolites by governing the inducible synthesis of different
classes of SMs in response to external stress stimuli. They bind to the promoter
region of the respective gene inducing an upregulation/downregulation in its
expression level. This chapter outlines the signalling pathways along with the
regulatory checkpoints that mediate the transcriptional modulation of secondary
metabolism in plants.
A. Gupta (✉)
Vinoba Bhave University, Hazaribag, Jharkhand, India
ICAR-Indian Institute of Agricultural Biotechnology, Ranchi, India
K. K. Gupta · P. K. Mishra
Vinoba Bhave University, Hazaribag, Jharkhand, India
S. K. Gupta
ICAR-Indian Institute of Agricultural Biotechnology, Ranchi, India
#
The Author(s), under exclusive license to Springer Nature Singapore Pte
Ltd. 2023
D. Singh et al. (eds.), Stress-responsive Factors and Molecular Farming
in Medicinal Plants,
https://doi.org/10.1007/978-981-99-4480-4_8
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124 A. Gupta et al.
Keywords
Secondary metabolites · Stress · Transcription factors · Biosynthetic pathways ·
Elicitors
Abbreviations
ABA Abscisic acid
DPF Diterpenoid phytoalexin factor
HMGR 3-hydroxy-3-methylglutaryl coenzymeA reductase
JA Jasmonic acid
MAPK Mitogen activated protein kinases
MEP 2-C-methyl-
D-erythritol 4-phosphate
NO Nitric oxide
ROS Reactive oxygen species
SA Salicylic acid
8.1 Introduction
Being sedentary in nature, plants opt to indigenous defensive mechanisms to cope
with different environmental stress (Seigler
2000). Secondary metabolites (SMs) act
as natural tools to help the plants in mediating this defense response. The SMs are
multi-functional plant metabolites that are not directly associated with the growth
and development of the plant rather they protect the plants against diseases, infection
or stress (Hartmann
2007). They are generally produced within the plants in small
quantities. However, the enhanced secretion of SMs during stress is elicited to confer
increased survival, durability and productivity to the host plant against the stress
stimuli (Jan et al. 2021
). The stress signals are initially perceived by the plant as
changes in the morphological traits and may vary depending on the variation in light,
temperature, moisture, salt concentration and soil fertility (Pradhan et al.
2017).
However, critically the stress response involves the activation of metabolic genes
concerned with the production of particular sets of SMs via the upstream signalling
pathways at the molecular level (Jamwal et al. 2018). This is because the immense
chemical diversity of the bioactive specialized metabolites and the availability of
complete genome sequences of the host plant sources invites great promise in
deducing the biosynthet ic mechanism of the metabolites (Saito
2013
). The synthesis
is largely concerned with the corresponding biosynthetic genes dispersed within the
genome of the plants (Field et al. 2011). The occurrence of stresses induces the
downstream differential expression of these genes with characteristic metabolomic
changes in the host plant (Dawid and Hille 2018). This in turn affects the synthesis of
the metabolites with respect to the severity of the associated stress. Therefore,
regulating these crucial mechanisms responsible for the synthesis of a particular
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metabolic trai t of interest seems essential towards the mitigation to different stresses.
In plants, this regulation is carried out by the corresponding transcription factors
(TFs) of the genes and the enzymes catalysing the biosynthesis (Yang et al. 2012).
8 Transcriptional Regulation in Biosynthesis of Phytochemicals in... 125
Generally, the plant response to
different abiotic stresses is governed by the
aromatic amino acids, which form the basis of SM biosynthesis in the shikimate
pathway followed by their conditional accumulation in different plant parts (Ahuja
et al.
2012). On the other hand, the response to biotic stresses is controlled by biotic
or abiotic elicitors, such as NO, ROS, Ca
2+
, plant hormones like JA, SA, ABA as
well as components of MAPK cascade that specifically produce molecules called
“mediators”, towards the adaptation to stressful conditions. These mediators then
trigger the activation of various TFs namely WAPK, MYB, NAC, AP2ERF and
bZIP/bHLH family. Further, these TFs mediate the regulated biosynthesis of differ-
ent classes of SMs, which may be either terpenes, flavonoids, S containing
compounds or N containing compo unds (Jan et al.
2021).
This chapter outlines the basic mechanism of biosynthesis of SMs in medicinal
plants mediated by a variety of TFs of marker metabolic genes responsible for the
development of stress tolerance in plants. Besides, it also signifies the application of
elicitors, such as exogenous, hormones to bring about the protection through TFs as
well as highlights the role of different omics techniques in pinpointing the regulatory
checkpoints in the overall complex and overlapping pathway.
8.2 Biosynthetic Pathways of SMs
There are several upstream metabolic signalling pathways that govern the down-
stream synthesis of the SMs under stress conditions. The initial is the primary
shikimate pathway, which synthesizes the aromatic amino acids namely tryptophan,
tyrosine and phenylalanine as primary metabolites and as the precursor molecules of
different classes of SMs (Parker et al.
2009). In this pathway, the primary reactant
shikimic acid is converted into the end-product chorismate in a series of seven-step
reactions (Maeda and Dudareva
2012). The aromatic amino acids are further pro-
duced from chorismate and are chiefly involved in protein synthesis and secretion of
phenolics group of SMs (Ahuja et al. 2012). Apart from the shikimate pathway, the
precursors of SMs are also synthesized within the Krebs cycle. Both these funda-
mental biosynthetic metabolic pathways remain conserved in most plants. In addi-
tion, the mevalonic pathway and the tricarboxylic acid cycle (TCA) pathway are also
involved in the biosynthesis of terpenes and nitrogen containing SMs respectively
(Jamwal et al. 2018).
8.3 Transcriptional Regulation of SM Biosynthesis Via TFs
The transcriptional regulation involved in the biosynthetic mechanism of SMs in
plants operates at various levels to govern the inducible synthesis of SMs (Yang
et al. 2012). This regulation is mediated by the TFs of the associated biosynthetic
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genes of the corresponding class of SMs. The TFs are basically DNA binding
proteins that alter the rate of initiation of transcription of the genes by RNA
polymerases (Jan et al. 2021). These factors tend to bind to the promoter regions
of target genes and regulate their expression via the integration of external and
internal signals (Yang et al.
2012). As a result of this differential expression of the
genes, different classes of SMs are conditionally accumulated in different plant parts
depending on diverse stress conditions. In this way, the TFs medi ate the inducible
synthesis of SMs via major signalling pathways namely the phenylpropanoid path-
way and the jasmonic acid pathway (Jan et al.
2021) as exemplified in the later
sub-sections. There are further different categories of TFs that have been identified to
regulate the biosynthesis of SMs under stress conditions.
126 A. Gupta et al.
8.3.1 WRKY TFs
The WRKY TFs family is the most widely studied category of TFs known to
participate in the modulation of stress-induced biosynthesis of SMs (Rushton et al.
2010). These are typically, proteins with a 60-amino-acid conserved domain that
interacts with the W-boxes present in the promoter sequence of the target genes
involved in a particular biosynthetic pathway (Cai et al. 2015). This class of TFs is
generally triggered in response to a wound or via jasmonic acid signaling and is
involved in the key synthesis of alkaloids, terpenoids and their subclasses (Phukan
et al.
2016). A list of WRKY TFs participating in the regulation of different SM
production in plants is discu ssed in Table
8.1.
8.3.2 MYB TFs
The MYB TF family plays an important role in regulating growth and reproduction
in plants apart from mitigation to stress conditions (Jan et al. 2021). The members of
this family are characterized by a DNA-binding domain that comprises of about
50–53 amino acids including four imperfect repeats of varied length (Dubos et al.
2010). Depending on their occurrence, these classes of TFs are further categorized as
R1, R2, R3 and R4 subclasses (Yamagishi et al. 2010). A study discussing the role of
MYBs in Arabidopsis thaliana mentioned that apart from enhancing the production
of SMs in plant species, AtMYBs have also been reported for reduced secretion of
kaempferol-3,7-dirhamnoside responsible for increased susceptibility to attack by
insects (Onkokesung et al.
2014). The MYB TFs are chiefly correlated to the
biosynthesis of proanthocyanins, flavonoids and HCAAs as exemplified in
Table 8.2.
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(continued)
8 Transcriptional Regulation in Biosynthesis of Phytochemicals in... 127
Table 8.1 Different members of WRKY family responsible for regulation of secondary metabolite biosynthesis in plants
TF family
Plant
species Responsible gene Pathway
Class of SM
involved Associated property Reference
WRKY3 and
WRKY6
Tobacco WRKY3 and WRKY6 Jasmonic acid Volatile terpenes Protection from attack by
Manduca sexta insects from
other feeding guilds
Skibbe
et al.
(2008)
AaWRKY1 Artemisia
annua
Sesquiterpene synthase gene,
ADS and GUS
Jasmonic acid Artemisinin Antimalarial Ma et al.
(2009)
StWRKY1 Potato 4-CL and THT Phenylpropanoid Hydroxycinnamic
acid amide (HCAA)
Late blight resistance,
secondary cell wall thickening
Yogendra
et al.
(2015)
TaWRKY70 Wheat ACT, DGK and GL1 Salicylic acid Hydroxycinnamic
acid amide
Resistance to fusarium
graminearum infection
Kage et al.
(2017)
HvWRKY23 Barley PAL, CHS and HCT Flavonoid and
lignin pathway
Hydroxycinnamic
acid amide and
flavonoid glycoside
Combat fusarium head blight Karre
et al.
(2019)
VviWRKY24 Vitis
vinifera
VviSTS29 Phenylpropanoid Resveratrol Protection against abiotic stress
and phytopathogens
Vannozzi
et al.
(2018)
SsWRKY18,
SsWRKY40
and SsMYC2
Salvia
sclarea
DXS, DXR, GGPPS and CPPS Plastidial
MEP-derived
terpenoid
pathway
Bietane-type
diterpene
Antibacterial and antifungal
properties
Alfieri
et al.
(2018)
WsWRKY1 Withania
somnifera
HMGS, HMGR, SQS, SQE,
FK, DWF1 and DWF5;
WsCYP93Id, WsCYP76A,
WsCYP98A, WsSGT1,
WsSGT2 and WsSGT4
Mevalonate and
MEP pathway
Phytosterol and
triterpenoid
withanolide
Tolerance to bacteria, fungi and
insects
Singh
et al.
(2017)
StWRKY8 Potato TyDC, NCS and COR2 MAPK pathway Benzylisoquinoline
alkaloid
Antimicrobial Yogendra
et
al.
(2017)
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Table 8.1 (continued)
TF family
Plant
species Responsible gene Pathway
Class of SM
involved Associated property Reference
ZmWRKY79 Maize An2 and ZmTPS6/11 Jasmonic acid
and ethylene
pathway
Terpenoid
Phytoalexins
Resistance to fusarium
graminearum infection,
phytohormone metabolism and
ROS scavenging
Fu et al.
(2018)
TcWRKY1 Taxus
chinenesis
Dbat Jasmonic acid Taxol Antitumour Li et al.
(2013)
CrWRKY1 C. roseus Tdc and Str Terpenoid indole
alkaloid pathway
Catharanthine Inhibition of
ABA and NO
scavenging
Chen et al.
(2013)
128 A. Gupta et al.
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8 Transcriptional Regulation in Biosynthesis of Phytochemicals in... 129
Table 8.2 Different members of MYB family responsible for regulation of secondary metabolite biosynthesis in plants
TF family
Plant
species Responsible gene Associated pathway
Class of SM
involved Associated property Reference
AtMYB113,
AtMYB114,
AtMYB75 and
AtMYB90
Arabidopsis
thaliana
PAP1, PAP2, Myb113
and Myb114
Phenylpropanoid
pathway
Anthocyanin
residues
Decreases pigmentation and
production of seeds of
normal color
Gonzalez
et al. (2008)
MYB-34,
MYB-51 and
MYB122
A. thaliana CYP79B2 and
CYP79B3
PEN 2 (penetration)
pathway
Indole
glucosinolate
Resistance to
Plectosphaerella
cucumerina
Frerigmann
et al. (2016)
CsMYBF1 Citrus plants CHS Phenylpropanoid
pathway
Hydroxycinnamic
acids and
flavonols
UV protection, antioxidant,
anti-inflammatory and anti-
proliferative capacities, anti-
cancer, radical scavenging
activity
Liu et al.
(2016)
CsMYB2/
CsMYB26
Tea
(Camellia
sinensis)
CsCHIT, CsGLUC.
CsPAL, C4H, 4CL,
CHI, DFR, F3H, F3,5H,
ANS, ANR
Flavonoid pathway Proanthocyanidins Tolerance against blister
blight disease
Nisha et al.
(2018)
MYB6 and
MYB12
Asiatic
hybrid lily
plants
LhbHLH1 and
LhbHLH2
Anthocyanin
biosynthetic pathway
Anthocyanins Against pigmentation Yamagishi
et al. (
2010)
AtMYB11,
AtMYB12 and
AtMYB111
A. thaliana AtZEP, AtNCED,
AtABA2, AtAAO,
AtP5CS and AtP5CR
ABA biosynthesis
pathway, proline
glutamate
biosynthesis pathway
Flavonoid, proline
and LEA proteins
ROS scavenging, salt and
drought tolerance
Wang et al.
(
2016)
MYB30,
MYB55
and
MYB110
Rice HCT, 4CL3, C4H and
PAL
Phenylpropanoid
pathway
HCCAs Enhance immunity, protects
against pathogens and
stressors
Kishi-
Kaboshi
et al. (2018)
PtMYB115 Poplar trees ANR1 and LAR3 Salicylic acid
signaling pathway
Proanthocyanin Resistance against
Dothiorella gregaria
Wang et al.
(
2017)
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