Plant secondary metabolites synthesis and their regulations under biotic and abiotic constraints

Abstract

Plants being sessile entities are often subjected to varied environmental stresses. They have developed an alternative defense mechanism that involves a vast variety of secondary metabolites to serve as tools to cope up with various stress conditions. The exposure of plant cells to abiotic and biotic stresses initiate multilevel reaction cascades that consequently leads to production and accumulation of various secondary metabolites. Various enzymatic and non-enzymatic molecules comprising the antioxidative defense system comes into play to counteract the undesirable effect of ecological stresses. Energy required as fuel in biosynthesis, transport and storage which comprises the costs for the formation of various transcription factors. When plant experiences stress in combination they express various transcription factors that might help the plant to make flexible signaling cascades to increase plant resistance against one of the stress. Based on this limelight, the present review aims to wrap the influence of different abiotic and biotic factors including salt, drought, heavy metals, UV light, herbivory and pathogenesis on secondary metabolites production and their roles in stress tolerance mechanism in plants.

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Vol.:(0123456789)
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Journal of Plant Biology (2020) 63:203–216
https://doi.org/10.1007/s12374-020-09245-7
REVIEW ARTICLE
Plant secondary metabolites synthesis andtheir regulations
underbiotic andabiotic constraints
ShubhraKhare1· N.B.Singh1· AjeySingh1· ImtiyazHussain2· KmNiharika1· VijayaYadav1· ChandaBano1·
RaviKumarYadav1· NimishaAmist1
Received: 7 September 2019 / Revised: 14 February 2020 / Accepted: 20 March 2020 / Published online: 8 April 2020
© Korean Society of Plant Biologist 2020
Abstract
Plants being sessile entities are often subjected to varied environmental stresses. They have developed an alternative defense
mechanism that involves a vast variety of secondary metabolites to serve as tools to cope up with various stress conditions.
The exposure of plant cells to abiotic and biotic stresses initiate multilevel reaction cascades that consequently leads to pro-
duction and accumulation of various secondary metabolites. Various enzymatic and non-enzymatic molecules comprising
the antioxidative defense system comes into play to counteract the undesirable effect of ecological stresses. Energy required
as fuel in biosynthesis, transport and storage which comprises the costs for the formation of various transcription factors.
When plant experiences stress in combination they express various transcription factors that might help the plant to make
flexible signaling cascades to increase plant resistance against one of the stress. Based on this limelight, the present review
aims to wrap the influence of different abiotic and biotic factors including salt, drought, heavy metals, UV light, herbivory
and pathogenesis on secondary metabolites production and their roles in stress tolerance mechanism in plants.
Keywords Secondary metabolites· Abiotic and biotic stresses· Reactive oxygen species· Antioxidative defense system
Introduction
Plant secondary metabolites (SMs) are natural byproducts
of primary metabolic processes. SMs have no direct role in
plant growth, metabolism and development but play a sig-
nificant role in plant defense mechanism, hence labeled as
‘secondary compounds’. The primary function of SMs is to
improve the growth and survival of the plants under adverse
conditions (Zandalinas etal. 2017). In mutualistic relation-
ships viz. pollination, legume root nodule and antagonistic
interactions viz. pathogenesis, herbivory SMs play a very
crucial role during communication (Chomel etal. 2016).
SMs are diverse group low of molecular weight miscellane-
ous compounds which are synthesized in low concentration
by large multimodular polyketide synthases (PKSs) and
nonribosomal peptide synthetases (NRPSs) or enzymes
such as prenyltransferases and dimethylallyl tryptophan
synthases (Brakhage 2013; Kasote etal. 2015). Accumula-
tion and production of SMs vary from species to species
or within the same plant species growing in different envi-
ronmental conditions (Radušienė etal. 2012). During the
growth of the plant different aspects including physiology,
genotype, stages of development and environmental factors
determines the concentration and types of SMs synthesis.
Biosynthesis of SMs is stimulated when plants are exposed
to various potential stresses at the expense of metabolic
energy (Eid etal. 2015). Plants are generally exposed to
various combinations of biotic and abiotic stresses, such
as drought, salinity, heavy metals, UV-irradiation, patho-
genesis and herbicides. Various Stresses alters morphology
and augments phenolic pigments level, antioxidant activity,
electrolyte leakage, flavonoids, proline, tocopherol accumu-
lation hampers plant growth (Brzezinska etal. 2006; Bano
etal. 2016, 2017) . In response to various biotic and abi-
otic stress ROS level enhanced in cellular system induces
oxidative stress which consequently leads to lipid peroxida-
tion, inactivation of enzymes and DNA damage (Akula and
* N. B. Singh
singhnb166@gmail.com
* Ajey Singh
ajey0408@gmail.com
1 Plant Physiology Laboratory, Department ofBotany,
University ofAllahabad, Prayagraj211002, India
2 Department ofBotany, Government Degree College, Kargil,
Ladakh, India

204 Journal of Plant Biology (2020) 63:203–216
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Ravishankar 2011). To overcome stress constraints plants
adopt many alternative mechanisms that involve a synthesis
of wide range of secondary products which serves as resist-
ance tools. An antioxidative defense system and different
metabolites help the plant to survive under adverse condi-
tion. The timely recognition of the stress by the plant is cru-
cial for a rapid and effective response. Intrinsic basal defense
mechanism is activated in plants as a result of stress recogni-
tion which in turn initiates complex signaling cascades of
defense varying from one stress to another (Chinnusamy
etal. 2004; Abou etal. 2009). The interaction and combined
exposure to various stresses are also possible. In response
to combined stresses, different signaling cascades shared
many intermediates compounds and outcomes. This could be
advantageous for creating a signaling network which helps
to enhanced resistance to abiotic stress under different biotic
stress. Hence lack of SMs and antioxidant enzymes synthesis
leads to long-term disrupted consequences in plants (Bar-
twal etal. 2013). Present review focuses on the biosynthe-
sis of SMs, SMs alteration made within plants in the levels
exposed to different abiotic and biotic stresses existing in
current environmental conditions.
Biosynthesis ofsecondary metabolites
inplants
Absence of immune system and mobility, plants synthesize a
wide range of secondary compounds. Under the unfavorable
condition, more than 100,000 SMs are produced in plants
from different metabolic pathways. The quantity and quality
of these compounds are greatly influenced by the growing
environment and temperature (Meena etal. 2017). The bio-
synthesis of SMs and their interconnections/interrelations
with primary metabolism inside the plant cell is shown in
Fig.1. A wide range of SMs are synthesized by alternative
mechanisms in plants and some common products are terpe-
nes, phenols, alkaloids etc. (Fig.1). Two major pathways for
the synthesis of terpenes are mevalonic-acid (MVA) path-
way and 2-C-methylerythritol 4-phosphate (MEP) pathways
Fig. 1 Biosynthesis of secondary metabolites and their interconnection with primary metabolites

205Journal of Plant Biology (2020) 63:203–216
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occur in cytosol and plastid, respectively. Product of glyco-
lysis such as pyruvate and glyceraldehyde-3-phosphate is
responsible for the synthesis of isopentenyl pyrophosphate
(IPP) and dimethylallyl pyrophosphate (DMAPP) which
act as a universal precursor for all terpenoids localized in
various cellular compartments (Fig.1). Terpenes synthase
enzyme are responsible for the synthesis of terpenes in dif-
ferent cellular compartments. Expression of different tran-
scription factors elevated under various abiotic and biotic
stresses such as in Daucus Carota and Bixa orellana, phy-
toene synthase and β-lycopene cyclase expression increases
the accumulation of carotenoids in response to salt stress
(Sankari etal. 2019; Simpson etal. 2018). Some other ter-
penes with their elevated transcription factors under various
biotic and abiotic stresses are mentioned in Table1. Phenolic
compounds are synthesized in plants using shikimic acid
pathway and the malonic acid pathway (Ghasemzadeh etal.
2011). Malonic acid pathway has been also reported in fungi
and bacteria for the synthesis of phenolics (Cheynier etal.
2013). Phenylalanine ammonia lyase (PAL) and CHS (chal-
cone synthase) are the soul enzymes regulate phenolic lev-
els under various stress constraints. Function of PAL, C4H
(cinnamate 4-hydroxylase), 4CL (4-coumarate:CoA ligase),
CHS, CHI (chalcone isomerase), F3H (flavanone3-hydroxy-
lase), F30H (flavonoid 30-hydroxylase), F3050H (flavonoid
3050-hydroxylase), DFR (dihydroflavonol 4-reductase), FLS
(flavonol synthase), IFS (isoflavone synthase), IFR (isofla-
vone reductase), and UFGT (UDP flavonoid glycosyltrans-
ferase) were upregulated with the elevated enzymes concen-
trations (Sharma etal. 2019). Nitrogen-containing SMs is
characterized by the presence of nitrogen molecule in their
structure and amino acids such as lysine, tyrosine and tryp-
tophan act as a precursor in their biosynthesis. Tryptophan
decarboxylase, WRKY6 and Hyoscyamine 6β-Hydroxylase
are some enzymes and factors responsible for the synthesis
of alkaloid under UV-B and salt stress, respectively (Schlut-
tenhofer etal. 2014; Mehrotra etal. 2018). Some other sec-
ondary metabolites under various biotic and abiotic stresses
are mentioned in Tables1 and 2.
Mobilization, accumulation andcost
ofsecondary metabolism andtheir
metabolites inplants
A group of SMs are accumulated constitutively in plant
tissues during metabolic processes. Vacuoles are reported
as a major storage site for various water-soluble SMs.
Different trapping mechanisms were used for storage of
various metabolites in vacuole such as isoquinoline alka-
loids by meconic acid or chelidonic acid in the latex vesi-
cles of Papaver or Chelidonium, respectively (Roshchina
etal. 2012). An adenosine triphosphate (ATP) dependent
transporter used to transport some xenobiotics and conju-
gated SMs such as glutathione into the vacuole (Wink 2003).
Proton gradient was generated by adenosine triphosphatase
(ATPase) located in tonoplast which is used as a driving
force by a proton antiport mechanism (Falhof etal. 2016).
Contrary lipophilic substances usually accumulated in tri-
chomes, resin ducts, glandular hairs, laticifers, thylakoid
membranes or on the cuticle and storage can also be tissue
and cell specific (Guern etal. 1987; Pagare etal. 2015).
Lipophilic compounds and some alkaloids such as berberine
are pumped across biomembranes with the help of a diverse
range of ABC transporters, a membrane protein driven by
ATP (Lv etal. 2016). H+-antiporter is used to mediate trans-
port of berberine to vacuoles instead of ABC transporters
(Otani etal. 2005). V-ATPase and V-PPase two proton pump
transporters located on the vacuolar membrane responsible
for uptake of SMs from the cytosol to vacuole by generat-
ing membrane potential difference (Roytrakul and Verpoorte
2007).
Energy required is contributed by H+-ATPase or ABC
transporters for the uphill transport across the tonoplast
and/or for trapping the metabolite in the vacuole (Buxbaum
2015). It was reported that alkaloid/H+ antiporters serve as
chief transporter for the transport of many alkaloids. In many
studies, it was reported that tannins, alkaloids or glucosi-
nolates stored in specific idioblasts (Mithöfer and Maffei
2016).Moreover, the biosynthesis of SMs, differentiations
and maintenance of special anatomical structures (ducts,
gland cells, trichomes) and sequestration (the corresponding
transcription and translation of related genes and mRNAs)
are expensive, required ATP or reduction equivalents, i.e.
nicotinamide adenine dinucleotide phosphate (reduced
formed) (NADPH2) (Wink 2011). In other words, it must be
costly for plants to produce defense and signal compounds.
Eect ofabiotic andbiotic stresses
onsecondary metabolism oftheplants
To cope up from different abiotic and biotic stresses such as
drought, salinity, heavy metals, UV-irradiation, herbivory
and pathogenesis plant synthesize various SMs as a result
of defense mechanism. Alterations in levels of different SMs
under abiotic and biotic stresses are mentioned in Tables1
and 2, respectively.
Eect ofsalt stress onsecondary metabolism
ofplants
The presence of excessive soluble salts in the soil is one the
major reason for the decline in crop yield and productivity
worldwide. Inspite of availability of water, high concentra-
tion of salt causes increase in ionic and osmotic stresses in

206 Journal of Plant Biology (2020) 63:203–216
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Table 1 Different secondary metabolites along with their transcription factors synthesized in plants under abiotic stress
Stress Secondary metabolites Source Transcription factor Function References
Drought stress Flavonoids Pisum sativum MYB Scavenging activity Larson (2018); Liu etal. (2016)
Rosmarinic acid Salvia miltiorrhiza SmPAL,SmC4H Significantly decreased both shoot
and root dry weight, but increased
the root to shoot ratio at later
growth cycle
Liu etal. (2011)
Chlorogenic acid Helianthus annuum HaHQT2 Protects against H2O2-induced
oxidative stress
Lubaina and Murugan (2013); Chee-
varungnapakul etal. (2019)
Epicatechins Camellia sinensis Chalcone synthase 1 and 3, antho-
cyanidin reductase 1 and 2 Anti-radiation and anti-aging Zhang etal. (2016)
Glycosides Scrophularia ningpoensis Decreased catalpol, harpagoside,
aucubin, harpagide, and cinnamic
acid content
Wang etal. (2006)
Salinity stress Abscisic acid Glycine max GmbZIP1 Improved tolerances Gao etal. (2011)
Sorbitol Lycopersicon esculentum Sorbitol-6-phosphate dehydroge-
nase (S6PDH)
Cell structure protection and
osmotic adaptation
Tari etal. (2010)
Polyamines Oryza sativa SAMDC Increase in polyphenol content Berberich etal. (2015); Do etal.
(2014)
Glycine betaines Triticum aestivum Betaine aldehyde dehydrogenase
(BADH)
Reduced membrane permeability
lipid peroxidation and H2O2
Yadav etal. (2017)
Tropane alkaloids Datura innoxia Hyoscyamine 6β-Hydroxylase Increase of scopolamine Kim etal. (2016); Schlesinger etal.
(2019)
Chlorogenic acid Helianthus annuum HaHQT2 Protects against H2O2-induced
oxidative stress
Lubaina and Murugan (2013); Chee-
varungnapakul etal. (2019)
Carotenoid Bixa orellana β-lycopene cyclase Act as a scavenger Sankari etal. (2019)
Carotenoid Daucus carota Phytoene synthase Photoprotective functions Simpson etal. (2018)
Rosmarinic acid Salvia miltiorrhiza SmPAL,SmC4H Significantly decreased both shoot
and root dry weight, but increased
the root to shoot ratio at later
growth cycle
Liu etal. (2011)
Heavy metal stress Flavonoids Vitis vinifera Chalcone synthase (CHS) and
flavanone3-hydroxylase (F3H)
Increased biosynthesis of phenolics Leng etal. (2015)
Artemisinin Artemisia annuaL. 3-hydroxy-3-methylglutaryl coen-
zyme A reductase
Reduced oxidative stress Rai etal. (2011a, b)
Chlorogenic acid Zea mays phenylalanine ammonia lyase
(PAL); Chalcone synthase; (CHS)
Reduced oxidative stress Kısa etal. (2016)
Essential oils Mentha pulegium L. 1-Deoxy d-xylulose-5-phosphate
synthase (Dxs)
Ameloirates harmful effects Nazari etal. (2017)
Apigenin Chrysanthemum morifolium Chalcone isomerase (CHI) Increased phenolic compounds
biosynthesis
Hodaei etal. (2018)

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crops which results in membrane disruption, high production
of ROS and ion toxicity (Ashraf etal. 2015). There have been
increased levels of tannic acid, flavonoids, and gossypol in
cotton plants exposed to salinity (Wang etal. 2015). In saf-
flower, under salt stress elevated levels of flavonoids, proteins
and soluble sugars were observed (Gengmao etal. 2015). The
tomato and mung bean plants exposed to differential levels of
salinity resulted in marked enhancement in carotenoids, phe-
nolics, and flavonoids content (Mahmood etal. 2016; Langi
etal. 2018). In Achillea fragrantissima, Catharanthus roseus,
Oryza sativa and Solanum nigrum higher alkaloid and phe-
nolic content exposed to salt stress which helps in scavenging
of harmful ROS (Verma and Shukla 2015; Chunthaburee etal.
2015; Ben Abdallah etal. 2016). Exposure of salt stress to
two sugarcane clones, i.e., CP-4333 (salt tolerant) and HSF-
240 (salt sensitive) showed decrease in flavones, anthocya-
nins, and soluble phenolics content although the decrease was
more in salt-sensitive HSF-240 clone (Parmar 2016). Essential
oil are ameliorating harmful effects and salinity triggered the
increased essential oils content in Salvia officinalis, Satureja
hortensis, and Matricaria recutita while it decreased in Men-
tha suaveolens, M. pulegium, S. officinalis, Matricaria chamo-
milla, Majorana hortensis, Origanum vulgare, Thymus maroc-
canus, Mentha piperita, and Trachyspermum ammi (Said-Al
Ahl and Omer 2011). Under salt stress condition altered lev-
els of SAMDC which enhances polyamine content in roots of
Helianthus annuus L. (Chiapusio etal. 2016).
Accumulation of various alkaloids like reserpine and vin-
cristine was observed under salt stress conditions in Rau-
volfia tetraphylla and Catharanthus roseus, respectively
(Said-Al Ahl and Omer 2011). Solanum nigrum seedlings
treated with various concentrations of salt viz 0, 50, 100 and
150mM significantly enhanced the expression of flavonoid
genes encoding flavonol synthase, chalcone synthase, and
phenylalanine ammonialyase, resulting in enhanced querce-
tin 3-β-d-glucoside, lutein, and lutein synthesis. Various
carotenoids related genes involving β-lycopene cyclase and
phytoene synthase 2 were upregulated on exposure to salt
stress (Ben Abdallah etal. 2016). ATPase, OSAP1 zinc fin-
ger protein, and transcription factor HB1B are some salinity
responsive genes expressed more in Pokkalia salt-tolerant
rice than in salt-sensitive rice line IR64 (Parihar etal. 2015).
GmERF057 and GmCAM4 are transcription factors play
a crucial role in tolerating and providing resistance to R.
solanacearum, Phytophthora sojae, Alternaria tenuissima,
and Phomopsis longicolla plants under salt stress (Rao etal.
2014).
Eect ofdrought stress onsecondary metabolism
ofplants
Plants subjected to water stress decreased water potential to
an extent that it affects the normal physiological processes
Table 1 (continued)
Stress Secondary metabolites Source Transcription factor Function References
UV-B stress Terpenes Vitis vinifera VvWRKY1 Increased tolerance to osmotic
stress
Marchive etal. (2013)
Terpenoids indole alkaloids Catharanthus roseus WRKY6 Transcription factor activity;
defense response
Schluttenhofer etal. (2014)
Phenolic compounds Clematis terniflora 5-enolpyruvylshikimate-3-phos-
phate synthase (CtEPSPS)
Elevate phenolics production Takshak etal. (2019)
Indole alkaloid Camptotheca acuminata Tryptophan decarboxylase Indole alkaloid biosynthesis Mehrotra etal. (2018)
Artemisinin Artemisia annuaL. 1-deoxy-D-xylulose-5-phosphate
reducto isomerase (DXR)
Act as scavenger Pandey and Pandey-Rai (2014)

208 Journal of Plant Biology (2020) 63:203–216
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(Salehi-lisar etal. 2012). Drought has a significant impact
on biochemical physiognomies of plants that affect plant
growth and development, photosynthesis, cellular dehydra-
tion and other metabolic processes. (Fig.2) (Xu etal. 2010;
Iqbal etal. 2011). Plants show a variety of responses related
to drought stress tolerance. In willow leaves, drought causes
oxidative stress which results in enhanced flavonoids and
phenolic acids contents (Larson 2018). The chlorophyll con-
tents decreased in cotton and Catharanthus roseus exposed
to drought stress (Akula and Ravishankar 2011). Saponin
contents in Chenopodium quinoa decreased in plants grow-
ing under low and severe water stress. It has been reported
that anthocyanins accumulate in plant tissues and provide
resistance against drought conditions (Morales etal. 2017).
In the root of Scutellaria baicalensis Georigi the expres-
sion of several flavonoids biosynthesis genes elevated under
drought stress (Yuan etal. 2012). In Antirrhinum majus
increased flavonoids accumulation resulted in the intense
purple coloration of both flesh and peel of fruit due to over-
expression of a basic helix-loop-helix (bHLH) transcription
factor gene AmDEL gene (Butelli etal., 2008). Arabidopsis
plants and wild type (WT) plants were exposed to drought
stress for 4weeks and resulted in a higher content of total
flavonoids in the tolerant transgenic plants in comparison
with WT plants due to increased AmDEL expression (Wang
etal. 2016).
Biosynthesis of SMs in medicinal plants like Artemi-
sia annua, Hypericum perforatum and C. roseus increased
several folds under water stress condition (Katz and Baltz
2016). Trachyspermum ammi grown in water limiting
fields showed a reduction in plant fresh and dry weight and
increased total phenolic content and pigments (Azhar etal.
2011). Drought stress showed elevated activity of antioxi-
dant enzymes (Amist etal. 2014, 2015) and enzyme activity
of proline metabolism in wheat plants (Amist and Singh
2014, 2015, 2017).
Under various stresses, including drought overexpression
of four basic leucine zipper (bZIP) gene family members,
GmbZIP44, GmbZIP46, GmbZIP62, and GmbZIP78, were
reported to enhance drought tolerance (Xie etal. 2009).
Overexpression of GmbZIP1 in BS93 a variety of Chi-
nese wheat under drought stress was used as an excellent
resource for genetic engineering of abiotic stress tolerance
in crop plants (Gao etal. 2011). Expression of some other
genes including GmNAC002, GmNAC010, GmNAC012,
GmNAC013, GmNAC015 and GmNAC028is induced in an
ABA-independent manner (Tran etal. 2009). In Lactuca
sativa the PAL gene activated under drought stress and
Table 2 Different secondary metabolites synthesized in plants under biotic stress
Stress Secondary metabo-
lites
Types Source Function References
Herbivory and patho-
genesis
Nicotine Pyridine alkaloid Nicotiana sp. Reduced bacterial
diversity and prevent
nectar spoilage
Stevenson etal. (2017)
Vindoline Alkaloid Catharanthus roseus Increase synthesis
monoterpene indole
alkaloids
DeLuca etal (1986)
Cholorogenic acid Phenol Vaccinium myrtillus Hamper growth of
lepidopteran larvae
Hernandez-Cumplido
etal. (2018)
Caffeoylquinic acids Phenylpropanoids Xanthiumpensylvani-
cium Act as antioxidants
and antibacterial
Miyamae etal. (2011)
Quinones Phenol Glycine max Defense against noc-
tuid larvae
Felton etal. (1994)
α-farnesene Terpene Malus domestica Olfactory behaviors
and the periodic-
ity of reproduction
of codling moth
females
Yan etal. (2003)
Amygdalin Cyanogenic glyco-
sides Prunus amygdalus Cause post-ingestive
malaise
Tiedeken etal. (2014)
Phytoalexin Diterpenoid Oryza sativa Induced resistance to
bacterial blight
Kanno etal. (2012)
Carboxyatractyloside Diterpene kaurene Xanthium cavanillesii Antimalarial Chen etal. (2015)
Quercetin Flavonoid glycosides Solanum nigrum Act as prooxidants
and are toxic to
several species of
lepidopteran
Schmidt etal (2005)

209Journal of Plant Biology (2020) 63:203–216
1 3
involved in the biosynthesis of various phenolics and flavo-
noids (Rajabbeigi etal. 2013). Exposure of C. acuminate, P.
somniferum camptothecin seedlings to water limiting condi-
tion enhances indole alkaloids such as narkotine, morphine
and codeine (Yang etal. 2018). In Catharanthus.roseusalka-
loid accumulation in shoot and root both increases due to
oxidative stress as compared with control plants (Jaleel etal.
2007). Underwater deficit condition in C. roseus,enhance
expression of betaine aldehyde dehydrogenase which
simultaneously uplifts glycine betaine (GB), synthesis an
osmolytes which play a protective role in the plant under
stress condition (Jaleel etal. 2007).
Eects ofheavy metals onsecondary metabolism
ofplants
Heavy metals stress is one of the main abiotic constraints
due to its high bioaccumulation and toxicity. Nowadays
heavy metals are frequently used in agarotechnics and vari-
ous developing industries. Heavy metals affect the qual-
ity and efficacy of natural products produced by plants.
Heavy metals stress impaired photosynthetic apparatus by
interact with protein of Light-harvesting complex II and
alter its conformation. Heavy metals stimulate senescence
by increasing ethylene synthesis followed by jasmonic acid
signaling pathway (Keunen etal. 2016). Artemisinin is a
sesquiterpenes synthesized in Artemisia annua L., when
treatment of As (0–4500μg L −1) was given. Futhermore, it
leads to synthesis and up regulation of various genes tran-
scripts such as 3-hydroxy-3-methylglutaryl coenzyme A
reductase, amorpha-4,11-diene synthase, cytochrome P450
monooxgenase and farnesyl diphosphate involved in arte-
misinin production (Rai etal. 2011a, b). Mentha pulegium
L. treated with 0–25mgkg −1 Cu and 0–50mgkg −1 Zn
concentrations increased synthesis of major components of
essential oils including pulegone, cis-isopulegone, α-pinene,
sabinene, 1,8-cineol, and thymol (Lajayer etal. 2017). Panax
ginseng Meyer and Withania somnifera L. Dunal at differ-
ent concentrations of Cu increased production of phenolic
and lignin compounds (Ali etal. 2006; Khatun etal. 2008).
Trigonella foenum-graecum L. when treated with Cd and Co
arouse production of diosgenin, whereas, Cr and Ni deter the
biosynthesis of diosgenin (Thomas etal. 2011). Hypericum
perforatum L. exposed to high concentrations of Ni i.e., 0.25
Fig. 2 Physiological changes in the plant under the influence of various abiotic and biotic stresses

210 Journal of Plant Biology (2020) 63:203–216
1 3
and 50μM resulted in inhibition of pseudohypericin and
hypericin synthesis and on the other hand at low concentra-
tions of Cr (VI) i.e., 0.01 and 0.1μM biosynthesis of total
hypericin was upregulated (Murch etal. 2003; Tirillini etal.
2006).
Eect ofUV stress onsecondary metabolism
ofplants
The UV-B wavelengths are potentially harmful and cause
deleterious effects on both plants and animals. Anthropo-
genic activities increased UV-B rays which cause DNA dam-
age and the formation of cyclobutane pyrimidine dimer in
plants (Fig.2). Plants also respond to small molecules of
different origin, known as elicitors that activate the same
response in the plant-like other stress conditions. These elici-
tors introduced in a cell in minute concentrations are capable
of redirecting the metabolism, causing increased formation
of particular SMs (Singla and Garg 2017). It has been shown
that in Catharanthus roseus exposed to UV-B light induced
the synthesis of dimeric terpenoids, strictosidine synthase,
indole alkaloids and tryptophan decarboxylasem RNA accu-
mulation (Ramani and Jayabaskaran 2008). In grapevine cell
cultures the outcome of UV irradiation on stilbene content
is lesser known (Tůmová and Tůma 2011). Accumulation of
stilbene in callus of grapevine treated with UV light resulted
in higher production of stilbene (including trans-resveratrol)
and it is found that only actively growing callus was capable
of producing stilbenes, whereas old callus had lost this abil-
ity (Tůmová and Tůma 2011). Clematis terniflora exposed
to120.8 Μw cm−2 UV-B dose following 36h of dark showed
an elevation in levels of genes involved in shikimate path-
ways such as shikimate kinase (CtSK), 5-enolpyruvylshiki-
mate-3-phosphate synthase (CtEPSPS), chorismate synthase
(CtCS), l-tryptophan synthase (l-CtTS), and l-serine deami-
nase (l-Ctsd) (Gao etal. 2016).
Under high UV radiation exposure in Clematis terniflo-
rathe genes and enzymes concerned with alkaloid biosyn-
thesis were upregulated to a greater extent in comparison to
control. 10-hydroxygeranioloxidoreductase (10-HGO) was
increased upto twofolds, the expression levels of mRNA
of 6–17-odeacetylvindoline O-acetyltransferase (dat),
tabersonine 16-hydroxylase (t16h), deacetoxyvindoline
4-hydroxylase (d4h), octadecaniod-derivative responsive
catharanthus AP2-domain protein 3 (ORCA3), strictosi-
dine synthase (str), geraniol-10-hydroxylase (g10h), and
10-hydroxygeraniol oxidoreductase (10-hgo) were over
expressed with t16h ORCA3 and str were enhanced upto
approximately fourfold (Gao etal. 2016). mRNA levels
of strictosidine β-glucosidase (sgd), secologanin synthase
(sls), and tryptophan decarboxylase (tdc) were upregulated
upon 30min of UV-B irradiation, but prolonged exposure of
up to 60min caused declination in there levels. Recently it
was reported that invitro propagated A. annua seedlings in
response to low UV-B dose (2.8 Wm-2), showed up-regula-
tion in genes like HMGR, 1-deoxy-d-xylulose-5-phosphate
reductoisomerase (DXR) (Table1), Isopentenyl pyroph-
osphate isomerase (IPPi), fernasyl diphosphate synthase
(FPS), ADS, cytochrome P450 dependent monooxygenase/
hydroxylase (CYP71AV1) and dihydroartemisinicaldehyde
reductase (RED1) leading to enhanced artemisin in accu-
mulation (Pandey and Pandey-Rai 2014).
Eects ofherbivory onsecondary metabolism
ofplants
Production of SMs that accumulate in plant tissues govern
a variety of diverse functions but principally for defense
against herbivores, fungi and bacteria and as plant signals
(Mithofer and Wilhelm 2012). Plants can have two ways to
avoid being eaten. First, they can avoid being selected for
oviposition or herbivory by synthesizing substances which
repel-ovipositing herbivores and attract enemies, includ-
ing predatory and parasitic insects by killing plant-feeding
insects which will reduce further damage. Secondly, by pro-
ducing chemicals responsible for the mortality of herbivores
(Mithöfer and Boland 2012). SMs regulates defense systems
in their interactions with insect herbivores, especially as tox-
ins or repellents, has been well established through decades
of research. Out of many SMs terpenes play a significant role
against herbivory such as conifers induce some additional
quantities of monoterpenes in response to bark beetle infes-
tation (Fig.2) (Xu etal. 2010). Pyrethroids (monoterpene
ester) and pyrethrins are strong insecticides found in leaves
and flowers of Chrysanthemum species and Tanacetum cin-
erariifolium,respectively, and are slight harmful to mam-
mals with their low tenacity in the environment (Xu etal.
2010). Recent research has revealed an interesting twist on
the role of the volatile terpenes where they play significant
roles in rice, cotton, wheat, sorghum and other species by
inducing certain monoterpenes and sesquiterpenes after
insect feeding (Smith 2005). Outward projection of glandu-
lar hairs from the epidermis having essential oil (a mixture
of volatile monoterpenes and sesquiterpenes) “advertise”
the toxicity of the plant and even a trial bite can reduce
the potential of herbivores. Azadirachtin is the most potent
feeding deterrent and it exerts a wide range of lethal effects
to herbivores (Saydee 2015).
Nectar and pollen SMs in many plants and their effect
on honey bees were studied: High nectar concentrations of
gelsemine (terpenoidal alkaloids) found in Gelsemium sem-
pervirens (nectar) associated with reduced pollen receipt
(Stevenson etal. 2017). Pollination of caffeinated flow-
ers enhanced with the production of caffeine due to better
recruitment and foraging on caffeinated food sources (Thom-
son etal. 2015). Damage on Glycine max foliage infected

211Journal of Plant Biology (2020) 63:203–216
1 3
with spider and mite elevate lipid peroxidation, lipoxygenase
(LOX), and peroxidase (POX), but the levels of the anti-
oxidant enzymes catalase (CAT) and superoxide dismutase
(SOD) were not affected (Heath etal. 2013). Nicotine, the
antagonist of nicotinergic acetylcholine receptors (nAChRs)
found in nectar and is involved in fast neurotransmission
between neurons (Moffat etal. 2016). Herbivores inhibit the
synthesis of toxic isothiocyanates from glucosinolates by
elevating the concentration of nitrile-specifier proteins and
sulfatases (NSPs) (Jeschke etal. 2015). However, the out-
come of these tactics is the breakdown of deactivated prod-
ucts that cannot be used for self-defense. By consequence,
inhibition of hydrolysis and non-disruptive feeding had done
by glucosinolate-sequestering insects by adapting strategies
to stabilize the toxins (Winde and Wittstock 2011).
In Chrysomela populi, ATP-binding cassette (ABC)
transporter (CpMRP) were identified expressing in defen-
sive glands and are involved in invitro transportation of
plant-derived phenolglucoside salicin (Strauss etal. 2013).
A recent research on Spodoptera littoralis moths found that
the herbivory-induced homoterpene (E)-4,8-dimethyl-1,3,7-
nonatriene (DMNT) inhibit moth responses and reduce vola-
tile organic compounds(VOC) emissions from green leaves
(Hatano etal. 2015). Sometimes a single compound such as
1-hexanol added to floral VOC bouquets and showed resist-
ance against Bombus sp. (Wright and Schiestl 2009).
Eect ofpathogenesis onsecondary metabolism
ofplant
Recognition of a variety of different pathogens, followed by
a diverse defense mechanism, plays a vital factor for plant
survival. The defensive mechanisms induced by pathogen
attack lead to an increased translocation of carbon skeletons
from source to site of infection which causes accumulation,
production and/or degradation of conjugates and /or de novo
synthesis of the SMs with protective or allelopathic activity
(Ayala etal. 2014).
For pathogenic interactions, SMs play crucial roles as
virulence factors, which can be observed for fungi infect-
ing animals as well as plants. Not only the role of SMs in
pathogenicity make them interesting to study, but many
SMs, including penicillin, statins, and cyclosporines, have
been found to have medical applications (Macheleidt etal.
2016). Against invading pathogens one of the most effective
and observable portions of defense mechanisms in nature
is hypersensitive reaction (HR) (Singh 2013). Persistence
and establishment of plants are greatly influenced by the
accumulation of secondary products in response to invading
pathogens (Rejeb etal. 2014). In fungi alteration in levels
of cyclic amino monophosphate (cAMP) regulatory ele-
ments greatly affects SMs synthesis with an enhanced rate
of PKA phosphorylation cause increase in sterigmatocystin
production in Aspergillus nidulans and orthologous path-
way mediates the biosynthesis of aflatoxin in A. parasiticus
and A. flavus (Thieme etal. 2018). Limonoids a nonvolatile,
bitter triterpenoids compounds found in citrus fruit, shows
lethal consequences by disrupting molting and other devel-
opmental processes of insects when ingested (Rao etal.
2017). Glucosinolates give characteristic smell and taste to
vegetables belonging to family Brassicaceae such as cab-
bage, broccoli, radish etc. and also show antimicrobial activ-
ity (Taiz and Zeiger 2006). Antiherbivore defenses due to
alkaloids and cyanogenic glycosides are well documented
(Mithöfer and Maffei 2016).
bZIP sand winged helix proteins are less frequently found
in fungi which often link stress response and SMs formation
(Hong etal. 2013). The winged-helix TF CPCR1 involved
in, arthrospore formation and cephalosporin C production,
thus links SMs synthesis and morphological development
(Macheleidt etal. 2016). In fungi, loss of LaeA and SMs
gene clusters causes a reduction in SMs production (Mache-
leidt etal. 2016). The tight regulation of light-dependent
sexual development and SMs formation shown in filamen-
tous fungi (Bayram and Braus 2012) is accomplished by
spatial compartmentalization of the velvet complex subu-
nits i.e., VelB and VeA (light-dependent), both can migrate
between the nucleus and the cytoplasm (Bayram and Braus
2012). Under darkness, VeA-VelB heterodimer is formed
and VeA moves to nucleus (Stinnett etal. 2007). The consti-
tutive nuclear localization of LaeA assists functional velvet
complex assembly only in the absence of light because light
suppresses the velvet-dependent functions in sporulation,
secondary metabolism and development (Brakhage 2013).
Cross talk signaling betweenbiotic
andabiotic stress
There is a great association between abiotic and biotic
stress, biotic stress can enhance the resistance to abiotic
stress (Abou etal. 2009). Transcription factors (TFs) play
an essential role in the stress response by directly regulat-
ing the expression levels of various stress-related genes. In
addition, to their ability for transcriptional regulation, TFs
play a key role in integrating diverse signaling pathways
in response to biotic and abiotic stresses. A number of
genes belonging to APETALA2/ethylene response factor
(AP2/ERF), MYB, WRKY, plant homeodomain (PHD),
NAC, bZIP and GT transcription factor (GT-1 binding site
related element binding factors) families in various model
systems have been demonstrated to play a pivotal role in
influencing stress-mediated cross talk in rice and Arabi-
dopsis (Mengiste etal. 2003; Vannini etal. 2006; Cao
etal. 2006; Nakashima etal. 2007; Chen etal. 2010; Zhu
etal. 2010; Liu etal. 2013; Xiao etal. 2013; Lindemose

212 Journal of Plant Biology (2020) 63:203–216
1 3
etal. 2013). GmDREB2 transcripts belonging to A5 gene
subclass were expressed in high salt, drought, cold and
ABA treatment (Gupta etal. 2016). When GmDREB2
transcripts overexpressed in Arabidopsis under the con-
trol of constitutive CaMV35S promoter or stress-induc-
ible responsive to dehydration 29A (RD29A) promoter,
the transgenic plants can survive up to a concentration of
200mM salt and drought stress and this effect is detect-
able when plants are under pathogen attack (Shin etal.
2019). Pathogen infection may cause stomatal closure to
obstruct the entrance of pathogen and as a result reduction
in water loss is observed and leads to an improved plant
resistance under abiotic stress (Atkinson etal. 2015). In
tomato plants, wounding enhances plant tolerance to salt
stress (Hu etal. 2017). In tobacco plants, ectopic expres-
sion of GmERF057 not only enhanced salt tolerance but
also increased resistance against bacterial pathogen Ral-
stonia solanacearum (Gupta etal. 2016).
The seedlings of Solanum lycopersicum infected by
Pseudomonas syringae pv. tomato (Pst) caused complete
resistance against insect Helicoverpa zea (Rejeb etal.
2014). Underwater deficit condition infection of tomato by
Botrytis cinerea and Oidium neolycopersici were reduced
(Rejeb etal. 2014). When stresses are given in combina-
tion common components and outputs are shared by dif-
ferent signaling cascades which could help plants to make
flexible signaling network and minimize energy costs
(Rasmussen etal. 2013; Koornneef and Pieterse 2014).
Xu and colleagues (2008) observed that plants infected
with virus showed resistance against drought stress.
The expression of several TFs belonging to MYB fam-
ily along with stress-responsive genes such as AZF1, STZ,
RHL41/ZAT12, and DREB2A and ABA signaling compo-
nents (LTP3, LTP4, PAD3, and UGT71B6) were raised in
transgenic plants (Xie etal. 2009). Overexpression of each
of these genes in Arabidopsis significantly improved plant
tolerance to drought, cold, and salinity stress. The plants of
Arabidopsis infected with Verticillium showed enhanced
tolerance towards drought due to expression of genes like
vascular-related no apical meristem. Cup-shaped cotyle-
don (NAC) domain (VND) in de novo xylem development
involved transcription factor VND7 which ensure water
storage ability in plants (Reusche etal. 2012). Ectopic
expression of GmbZIP44, GmbZIP62, and GmbZIP78 in
Arabidopsis results in reduced sensitivity toward ABA
compared with WT plants at the germination stage (Gupta
etal. 2016). Combined stress of heavy metals and patho-
gens enhances the expression of defense enzymes such
as glucanases, chitinases or proteinases (Mithöfer and
Wilhelm 2012). Mittra etal. (2004) observed that plant
showed resistance against fungal and viral infection when
pre-exposed to mild concentrations of Cd.
Conclusion andfuture prospective
SMs are natural products induced in plants exposed to vari-
ous potential enemies. These compounds serve to meet the
secondary requirements of the producing organisms. Growth
and productivity of crop plants were adversely affected by
various biotic and abiotic stresses. These secondary com-
pounds play defensive roles in plants under various abiotic
and biotic constrains and play a promising role in adapting
plants to their local environment. They mediate a variety
of defensive functions by elevating the synthesis of various
enzymes responsible for SMs production and enhance the
expressions of various genes involving in resistance mecha-
nism of the plants. Ecological factors which influence SMs
production and elevate their potential to over produce useful
phytochemicals for varied applications. Invitro plant cell
culture used for the production of synthetic biochemicals
and drugs has made new footsteps in the world of natu-
ral products. A Recombinant DNA technology is used for
commercial production of SMs on the basis of the regulated
pathway of secondary metabolism via genetical tools. For
substantial interest in plant harvesting, large-scale plant
cell culture technology will be used for the utilization of
SMs due to its medicinal properties and supply concerns.
Moreover, molecular understanding will help to under-
stand different stress responses useful in plant development
with enhanced adaptation and efficiency. Although various
researches have been done but it is interesting to focus our
future studies on understanding how different ecological sig-
nals affect biosynthesis of various SMs. Future research in
the field of bioinformatics could help to decode the produc-
tion of various SMs at cellular and molecular levels.
Acknowledgements The authors are thankful to the University Grant
Commission (UGC), New Delhi, India and University of Allahabad,
India for providing financial assistance to Shubhra Khare.
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