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date: 24 November 2020

Tomatoes: A Model Crop of Solanaceous Plantsfree

  • Raheel Anwar, Raheel AnwarUniversity of Agriculture Faisalabad
  • Tahira FatimaTahira FatimaPurdue University, Department of Horticulture and Landscape Architecture
  •  and Autar MattooAutar MattooUnited States Department of Agriculture


The modern-day cultivated and highly consumed tomato has come a long way from its ancestor(s), which were in the wild and not palatable. Breeding strategies made the difference in making desirable food, including tomato, available for human consumption. However, like other horticultural produce, the shelf life of tomato is short, which results in losses that can reach almost 50% of the produce, more so in developing countries than in countries with advanced technologies and better infrastructure. Food security concerns are real, especially taking into consideration that the population explosion anticipated by 2050 will require more food production and the production of more nutritious food, which applies as much to the tomato crop as the other crops. Today’s consumer has become aware and is looking for nutritious foods for a healthful and long life. Little was done until recently to generate nutritionally enhanced produce including fruits/vegetables. Also, extreme environments add to plant stress and impact yield and nutritional quality of produce. Recent developments in understandings of the plant/fruit genetics and progress made in developing genetic engineering technologies, including the use of CRISPR-Cas9, raise hopes that a better tomato with a high dose of nutrition and longer-lasting quality will become a reality.


The tomato has become an important vegetable/fruit of high economic value worldwide due to its status as a high-yielding (37.6 tons/hectare) crop among other commonly consumed vegetables (Table 1), with its tasty fruit and richer dose of healthful nutrients and particularly its carotenoid/lycopene content (Table 2) and it amenability as a homegrown (kitchen/home gardening) vegetable. Among the top 10 vegetables produced in the world, tomato ranks at the top and is one of the highest traded commodities (Table 1). Fresh tomatoes are consumed in salads. Minimally processed tomatoes are available in canned or crushed forms, whereas fully processed tomatoes include juice, ketchup, paste, purée, and sauce. In most countries, it constitutes a major food component of the daily diet.

Major tomato-cultivating countries that are responsible for 61% of the world’s tomato resources include China (33%), India (11%), Turkey (7%), the United States (6%), and Egypt (4%) (Figure 1). Other high-producing countries are Iran, Italy, Spain, Mexico, Brazil, Nigeria, and Russia. In 2016, the global export of fresh and processed tomatoes generated US$12.8 billion in revenues, while by 2017 total tomato production in the world reached 182.3 million tons from 4.8 million hectares. Mexico, the Netherlands, and Spain were the top three tomato-exporting countries, with an export share of 22%, 13%, and 12%, respectively (Figure 2). Other major exporting countries of fresh tomato include Morocco, Turkey, Jordan, India, France, Belgium, and the United States. Among these, the United States is not only the 10th-ranked tomato-exporting country but also ranked among the top fresh tomato-importing countries (Figure 2). Norway, Finland, Switzerland, Ireland, Sweden, Germany, Denmark, Austria, and Canada were among the top 10 importing countries in 2016; the imported fresh tomato costs them from US$2,475 to 1,611 per ton (2016 trade statistics, Figure 3). Thus, the tomato is an economically important crop the world over. Its demand has also created a need to produce newer, high-yielding varieties with better nutritional quality.

Figure 1. World tomato production map with percentage contribution of each country.

Data extracted from FAO (2017). Name or percentage share of only a few countries is highlighted for reference.

Figure 2. World tomato exporting and importing countries with percentage contribution of each country in trade volume.

Data extracted from FAO (2016).

Figure 3. World importing countries paying top price per ton. Only countries importing more than 10,000 tons are included.

Data extracted from FAO (2016).

The wild tomato plant originated from the warmer areas of South America, including Ecuador, Chile, and the Galapagos Islands (Peralta & Spooner, 2007; Robertson & Labate, 2007; Rothan, Diouf, & Causse, 2018), with Peru as its center of origin. Based on its physical characteristics, the tomato was placed alongside the potato in the genus Solanum (Linnaeus, in 1753); however, Philip Miller placed it in a new genus and called it Lycopersicon esculentum. Lycopersicon esculentum Mill. is considered as a progenitor of large-fruited cultigens (Bailey, 1896; Robertson & Labate, 2007). Molecular phylogeny resolved the taxonomic status and placed tomato back under the genus Solanum, viz., Solanum lycopersicum L. (Peralta, Knapp, & Spooner, 2006). Cultivation, selection, and domestication of tomato species have been practiced since the dawn of civilization.

The tomato as a perishable horticultural crop has become an established model system for studying the intricate nuances of fleshy fruit development, including the ripening, postharvest, and senescence stages. It is sensitive to temperatures below 10ºC (leading to chilling injury) and above 28ºC (leading to heat stress), which cause damage. This precludes the use of cold storage for longer periods as well as long-distance transportation during hot summers, causing serious losses of tomato. Such postharvest losses create an obstacle to food security and economic losses during storage and long-distance shipping/transportation. The science of postharvest physiology and biochemistry of fruits/vegetables, including tomato, has transitioned in recent years with the advent of advanced molecular and biochemical approaches.

Table 1. Nutrient Facts of Fresh Tomato






94.52 g


0.594 mg


18 kcal

Vitamin B-6

0.08 mg


0.88 g

Ascorbic acid (vitamin C)

13.7 mg

Total lipid (fat)

0.2 g

Folate, total

15 µg


3.89 g

Folate, food

15 µg


1.2 g

Folate, DFE

15 µg


2.63 g

Choline, total

6.7 µg

Calcium (Ca)

10 mg

Vitamin A, RAE

42 µg

Iron (Fe)

0.27 mg


449 µg

Magnesium (Mg)

11 mg


101 µg

Phosphorus (P)

24 mg


2573 µg

Potassium (K)

237 mg

Lutein + Zeaxanthin

123 µg

Sodium (Na)

5 mg

Vitamin E (α‎-tocopherol)

0.54 mg

Zinc (Zn)

0.17 mg

Vitamin K (phylloquinone)

7.9 µg

Copper (Cu)

0.059 mg

Fatty acids, saturated

0.028 g


0.037 mg

Fatty acids, monounsaturated

0.031 g


0.019 mg

Fatty acids, polyunsaturated

0.083 g

* Amounts per 100g Fresh Weight. Note. No amount of selenium, folic acid, vitamin B-12, retinol, β‎-cryptoxanthin, Vitamin D, cholesterol, ethyl alcohol, caffeine, or theobromine could be detected in fresh tomatoes (USDA, 2019).

Source. USDA (2019).

Table 2. Production, Area, and Yield of Top 10 Vegetables in the World



Production (million tons)

Area (hectares)

Yield (tons/hectare)







Onion (dry, shallots)





Cucumber, Gherkin





Cabbage, Other Brassicas





Eggplant (Aubergine)





Carrots, Turnips





Chillies, Pepper (green)















Pumpkins, Squash, Gourds










Source. FAO (2017).

These developments in understanding the players involved in tomato (fruit) biology and senescence can contribute to strategies for improving production, curtailing the losses due to short postharvest life and eventually the ability to manipulate the ripening process. A major hormone that regulates fruit ripening is ethylene, also called the “ripening hormone.” More is now understood about how ethylene induces ripening, its signal transduction pathway, and its interaction with other plant hormones in the process (Anwar, Mattoo, & Handa, 2019; Fatima et al., 2008; Harpaz-Saad, Yoon, Mattoo, & Kieber, 2012; Klee & Giovannoni, 2011; Mattoo & Handa, 2017; Nath, Bouzayen, Mattoo, & Pech, 2014). Advanced biotechnology and bioinformatic tools have helped to mine the data from studies involving genetically engineered lines and natural mutants of tomato, and the information generated has added to current understandings of the players that regulate tomato fruit ripening. Thus plant hormones, various transcription factors, small metabolites, micro RNAs (miRNAs), epigenetic factors, and other factors interactively regulate tomato fruit ripening (Anwar et al., 2019; Bapat et al., 2010; Bouzayen, Latche, Nath, & Pech, 2010; Handa, Anwar, & Mattoo, 2014; Klee & Giovannoni, 2011; Osorio & Fernie, 2013; Osorio, Scossa, & Fernie, 2013; Seymour, Chapman, Chew, & Rose, 2013; Seymour, Poole, Giovannoni, & Tucker, 2013). Scientists now have new toolsets available for improving the quality, flavor, taste, and shelf life of tomato. On the other hand, it has also become apparent that developing a tomato germplasm that is resistant to a variety of biotic and abiotic stresses is not easily achievable using simple and normal breeding strategies. This is so because these traits are not singular and are rather more complex than previously thought.

There is a need not only for developing tomato lines with higher fruit yield, longer shelf life, and greater resistance to biotic and abiotic stressors but also for enhancing the levels of health-promoting nutrients (Causse, Giovannoni, Bouzayen, & Zouine, 2016; Kaur, Handa, & Mattoo, 2017). The educated consumers’ demand for nutritionally enriched fruits and vegetables has intensified, particularly for tomatoes. However, these nutrients are often present in tomato fruit at only marginal concentrations for human nutrition/prevention of disease. The nutrient load is primarily dependent on crop genetics and is regulated by complex developmental and environmental cues (Roberts & Mattoo, 2019). Vitamin C (ascorbic acid) is an essential nutrient in the human diet (Mellidou & Kanellis, 2017). Green tomato fruits contain relatively high amounts of total ascorbic acid (23.4 mg per 100 g), which decreases to 13.7 mg per 100 g in red ripe tomatoes (USDA, 2019) (Figure 4).

Figure 4. Growth habit of tomato plants, i.e., indeterminate plants (left) and determinate plants (right). Indeterminate tomato plants are generally grown under structures where vines can be trained on hanging strings while determinate plants are low statured and can be grown in open fields.

Although commercially cultivated tomato varieties (Solanum lycopersicum accessions) are considered a good dietary source of ascorbic acid, tomato’s wild progenitors such as Solanum pennellii have much higher ascorbic acid content (47.5 mg per 100 g) (Di Matteo et al., 2010). This means that ascorbic acid gradually declined during selection and domestication of tomato genotypes. On the other hand, phytonutrient lycopene, an important carotenoid that provides red pigmentation of ripe tomato fruit, is known for its antioxidant/anticancer properties (Giovannucci et al., 2002). However, its levels are not sufficient for a good dietary dose. Lycopene-enriched and longer shelf-life tomato fruit (Mehta et al., 2002) and anthocyanin-rich tomatoes (Butelli et al., 2008) have been genetically engineered. However, more needs to be done to provide the consumer with a tastier tomato enriched with a high dose of healthful compounds for a healthy life.

Agronomic Aspects of Tomato Production

Tomato is a commonly grown vegetable in most countries, and the production systems employed include open field, tunnels, net house, greenhouses, and soilless culture, like hydroponics. Its growth habit can vary to be determinate or indeterminate (Figure 5).

Figure 5. Endogenous levels of ascorbic acid during tomato fruit maturation.

Data is adapted from USDA Food Composition Databases (USDA, 2019).

Determinate tomatoes flower almost at the same time, contain a predetermined number of clusters, and grow to small heights. Indeterminate tomato plants keep growing and produce flower clusters until the weather prohibits (tomato plants are sensitive to cooler temperatures such as below 10º–15ºC). Indeterminate plants need more plant care than determinate ones; the older leaves on the lower part of the growing stem need to be excised, while the continuously elongating stems need support with strings so that they do not droop and fall to the ground. Indeterminate varieties have higher yields than the determinate types. Indeterminate varieties are generally managed on strings under tunnels or in a greenhouse, whereas determinate tomato plants are usually grown in open fields.

Tomato is a warm season crop. Therefore, during the off-season (cooler temperatures), farmers the world over have the opportunity to invest in a tunnel system for off-season production of tomatoes. Such a production business has gained popularity. Off-season harvest generally hits the market when open field production has yet to arrive. Tomato plants grown under protective structures are generally uniform in size and quality and give consistent yield for an extended period. Because tomato crops are sensitive to frost injury, transplantation of tomato seedlings in the open field is started only after the frost spell. They are mostly grown in loamy soils during the dry season. During early growth, proper weed management and moist soil around seedlings favors a quick crop stand. A good mulch (preferably legume based) under the plant canopy enables the soil to remain moist and deters weed growth. In mechanized countries, tomatoes are grown in open field, harvested mechanically all at once, and then transported in bulk, whereas indeterminate varieties are generally preferred for fresh market tomatoes as these are juicier. Since indeterminate varieties keep producing flowers and fruits, they require multiple picking, usually by hand. Due to the demand for indeterminate varieties, farmers have started growing indeterminate tomato plants in open fields using various support systems such as strings or wire nets.

From Flowering to Fruit Development to Ripening

Flowering is a genetically programmed event in angiosperms in which seeds are enclosed in an ovary. Factors such as endogenous molecules, environmental cues, production practices, and/or external stressors can alter the timing and intensity of the floral transition. Since the time of tomato domestication, genetic mutations in growth factors that control the flowering in response to internal and external cues led to the expansion of tomatoes beyond their native geographical locations. Today more is understood about the key elements and genetic players that impact the life of a plant from vegetative growth to flowering to fruit development to fruit ripening, due largely to advances in biotechnology and genetics. Progress toward developing toolsets of engineered genes and metabolic pathways have contributed to current understandings about plant life at large and plant processes in general. For example, plant switching from the vegetative to the reproductive phase involves floral transition of the shoot apical meristem and development of inflorescence architecture, which are controlled by regulatory interactions of several genetic factors (Huang et al., 2018; Périlleux, Lobet, & Tocquin, 2014; Silva Ferreira et al., 2018; Xu, Park, Van Eck, & Lippman, 2016). Identification of transcription factors that have specific binding sites on cognate gene(s) has added to knowledge of how genes are regulated. For example, transcription factor AGAMOUS-LIKE1 (TAGL1) regulates sepal and carpel size (Vrebalov et al., 2009). Thus an florigen paralog and flowering repressor SELF PRUNING 5G (SP5G), not expressed in cultivated varieties, was found to be highly expressed in the long-day wild tomato. Meanwhile, a scientific breakthrough led to a new genome editing toolset called CRISPR/Cas9, which can change gene function by altering DNA sequence in a highly specific manner (reviewed in Lander, 2016). Utilizing the CRISP/Cas9 technology to silence the SlSP5G gene in tomato led to more compact growth, initiation of early flowering, and earlier harvesting of the engineered tomato fruit (Soyk et al., 2016).

Fruit development is the terminal stage in plant ontogeny. Selection and domestication of the wild small fruiting tomato ancestor Solanum pimpnellifolium that led to present-day commercially grown tomato cultivars also brought about evolution of diversity in tomato fruit shape and size. Utilizing this genetic diversity enabled identification and characterization of two genes regulating variation in weight (FW2.2, FW3.2) and four genes (SUN, OVATE, LC, FAS) that regulate the shape of tomato fruit (van der Knaap et al., 2014, and references therein). Glucose and hormones, mainly auxin, gibberellins, and cytokinin, are vital for fruit set (Kumar, Khurana, & Sharma, 2014; Liu et al., 2018; Ruan, Patrick, Bouzayen, Osorio, & Fernie, 2012). Hormonal signaling and carbon partitioning also tightly control rapid division and expansion of cells as well as dramatic shifts in metabolic profiles in expanding fruits. This phase is also marked by the accumulation of phenolic compounds, soluble solids, organic acids, and anthocyanins (Dardick & Callahan, 2014; Handa, Tiznado-Hernández, & Mattoo, 2012; Hiwasa-Tanase & Ezura, 2014; Klie et al., 2014; McAtee, Karim, Schaffer, & David, 2013; Seymour, Østergaard, Chapman, Knapp, & Martin, 2013). A blend of these metabolites in edible tissues of tomato (epicarp, septum, and interlocular tissues) can determine nutritional and sensory quality of a red ripe tomato. From a consumer perspective, sweetness, glutamic acid, titratable acidity, and juiciness are major quality benchmarks (Casals, Rivera, Sabaté, Romero del Castillo, & Simó, 2018), in addition to health-promoting benefits of several nutrients present in tomato.

The final phase of tomato plant development leads to a red ripe fruit and the photosynthesizing organelle chloroplast transitions into an organelle called chromoplast, in which human health promoting carotenoids including lycopene and β‎-carotene accumulate. Lycopene forms 70% to 90% of total carotenoids present in tomato fruit and, as stated earlier, is the reason for the red color of ripe tomato fruit, whereas β‎-carotene content forms 5% to 40% of total carotenoids contributing the orange color of tomatoes (Burns, Fraser, & Bramley, 2003; Ronen, Carmel-Goren, Zamir, & Hirschberg, 2000). Phytochrome pigment is involved in photomorphogenesis, and phytochrome-interacting factors trigger biosynthesis of carotenoids—lycopene, carotenes, zeaxanthin, and lutein—as well as the carotenoid-derived volatiles (Fantini, Falcone, Frusciante, Giliberto, & Giuliano, 2013; Llorente, D’Andrea, & Rodríguez-Concepción, 2016; Seymour, Østergaard, et al., 2013; Tomato Genome Consortium, 2012). During tomato fruit maturation, the carotenoid synthesis enzyme phytoene synthase 1 (SlPSY1) is inhibited via direct interaction with the STAY-GREEN protein (SlSGR1) to regulate chlorophyll degradation in tomato leaves and fruit. In this colors-changing scheme, one other master fruit-ripening regulator called SlMADS-RIN controls PSY function (Fujisawa, Nakano, Shima, & Ito, 2013). Thus the tomato fruit undergoes changes in pigmentation upon ripening from a green (chlorophyll intense) and solid mature fruit to red (or orange) (chromoplast intense) fruit. β‎-carotene is utilized in the synthesis of vitamin A and another hormone called abscisic acid (ABA). The life of a transforming and transitioning tomato fruit from green to red is coordinated by interactions of various but specific gene players, including small heat shock protein (HSP21) (Neta-Sharir, Isaacson, Lurie, & Weiss, 2005), and may involve light (via reduction in the expression of ETHYLENE RESPONSE FACTOR E4 [SlERFE4]) and upregulation of both AUXIN RESPONSE FACTOR 2 paralogues (SlARF2a/b) (Cruz et al., 2018).

Ethylene: A Fruit-Ripening Hormone

The dissipation in green color at the onset of the tomato fruit ripening phase is associated with a climacteric burst in respiration (involving the enzyme alternate oxidase) and ethylene production (Cherian, Figueroa, & Nair, 2014), transformation of chloroplasts into chromoplasts, and loss of photosynthetic membrane integrity (Yazdani et al., 2019). Ethylene is a gaseous hormone fundamental to the fruit ripening process in many fruits, including tomato. In addition to ethylene, other developmental factors also contribute to tomato fruit ripening. Fruit characteristics are irreversibly altered due to pigmentation and alteration in volatile and bioactive compounds (carotenoids, anthocyanin, flavonoids, volatiles, lipids, etc.) and changes in cell wall integrity and cellular constituents (Bouzayen et al., 2010; Handa et al., 2014; Handa, Srivastava, et al., 2010; Klee & Giovannoni, 2011; Osorio et al., 2012; Osorio et al., 2013; Valero & Valero, 2013). Dynamic morphological and biochemical changes in a ripening fruit are spatiotemporally regulated by various transcription factors, signaling molecules/hormones and their crosstalk at genetic and epigenetic levels (Giovannoni, Nguyen, Ampofo, Zhong, & Fei, 2017).

Ethylene production during plant growth and development has two distinct phases called “system 1” and “system 2.” Ethylene production in vegetative tissues and unripe fruits is regulated in an autoinhibitory manner, which maintains its basal level; this mode of ethylene synthesis is system 1. On the other hand, ethylene is produced at higher levels during flower senescence and fruit ripening; this mode of ethylene synthesis is autocatalytic and known as system 2. Climacteric fruits, such as tomato, exhibit a simultaneous burst in ethylene production, which is its major role as a fruit-ripening hormone. Intricate details about production, perception, and mode of action of ethylene and what regulates fruit ripening are now known. The enzyme 1-aminocyclopropane-1-carboxylate synthase (ACC synthase) is critical for the synthesis of 1-aminocyclopropane-1-carboxylate (ACC), which is the immediate precursor of ethylene. ACC is oxidized by the terminal enzyme called ACC oxidase (ACO) to produce ethylene. The importance of these two molecules in ethylene biology is apparent from the fact that at least nine ACS (ACS1A, ACS1B, ACS2-8), five ACO (ACO1-5), six ethylene receptors (ETR1, ETR2, ETR4, ETR5, ETR6, ETR3/Never-ripe), and four EIN3-like (EIL) genes have been identified that orchestrate ethylene signaling cascade (see Paul, Pandey, & Srivastava, 2012, and references therein). A global view of transcriptional network and temporal changes of ethylene-responsive genes in tomato fruit development/ripening is also available (Liu, Yu, et al., 2015; Sharma et al., 2010). Ethylene also coordinates with other ripening-related developmental factors, namely, auxin, ABA, RIN, NON-RIPENING (NOR), CNR, and TAGL1, to regulate different processes during plant and fruit development (Mou et al., 2016; Osorio et al., 2011). Three types of transcriptional feedback circuits proposed to control ethylene-dependent ripening in climacteric fruits such as tomato are MADS-type circuit, peach NAC-type circuit, and banana dual-loop circuit (Lü et al., 2018). 1H-nuclear magnetic resonance spectroscopy was employed to dissect metabolic pathways that are ethylene-dependent or ethylene-independent in unique “transgenic” tomato lines, one with impaired expression of ACC synthase-2 gene and the other a progeny of its genetic cross with a line overexpressing yeast S-adenosylmethionine decarboxylase (Sobolev et al., 2014). It enabled the identification of ethylene-dependent metabolites (increase in amino acids glutamate and aspartate plus adenosine monophosphate [AMP]) and those that were ethylene-independent (alanine, tyrosine, valine, isoleucine, phenylalanine, malic acid, and myo-inositol). Such approaches are important for modifying metabolic pathways to either add a dose of nutrients to a produce (tomato fruit) or reduce unwanted or antinutrition molecules.

Hormones Abscisic Acid, Auxin, and Polyamines Have a Stake With Ethylene in Fruit Ripening

In addition to ethylene, the hormone ABA has a say in controlling ripening in tomato since the climacteric burst of ethylene was found to be accompanied by a sharp increase in ABA content (Leng, Yuan, & Guo, 2014). Exogenous ABA application promoted not only the expression of ethylene regulators (RIN, TAGL1, CNR, NOR) but also those involved in ethylene production and response (ACS4, ACO1, GR and ETR6) (Mou et al., 2016; Zhang, Yuan, & Leng, 2009). Reciprocally, ethylene is required for the induction of ABA synthesis (Mou et al., 2016). Opposite to ethylene and ABA, another plant hormone, auxin (IAA), delays fruit ripening via impact on ripening regulators (RIN, ethylene, and ABA) and biosynthesis of lycopene and β‎-xanthophyll (Su et al., 2015). Out of 25 identified Aux/IAA genes in tomato, five (IAA3, IAA4, IAA9, IAA15 and IAA27) mingle with fruit ripening (Audran-Delalande et al., 2012). Light is a factor for carotenoid (nutrition) accumulation by repressing these Aux/IAA genes (Cruz et al., 2018). AUXIN RESPONSE FACTOR 4 (ARF4/DR12) was found to promote catabolism of starch into glucose and fructose pinpointing role of auxin in essential cellular processes in tomato fruit (Dai et al., 2016; Jones et al., 2002; Sagar et al., 2013).

Polyamines are ubiquitous natural plant growth regulators among which the most studied include putrescine, spermidine, spermine, and thermo-spermine (Mattoo, Fatima, Upadhyay, & Handa, 2014; Mattoo, Minocha, Minocha, & Handa, 2010). Using a genetic engineering approach enabled accumulation of spermidine and spermine levels at the cost of putrescine in transgenic tomato (Mehta et al., 2002). These tomatoes were not only much richer in properties such as the anticancer carotenoid lycopene but also had better firmness and high juice viscosity, attributes that reinforced the promotive role of spermidine/spermine in improving tomato nutrition and quality (Handa, Nambeesan, et al., 2010; Kolotilin et al., 2011; Mehta et al., 2002; Nambeesan et al., 2010; Srivastava et al., 2007). Cross-linkages of polyamines with other plant hormones were found to be prevalent based on collation of transcriptomic data from different tomato genotypes (Anwar, Mattoo, & Handa, 2015). Thus polyamine crosstalk with plant signaling hormone genes was unraveled. Spermidine was found to be negatively linked with ABA biosynthesis but positively linked with genes for the biosynthesis of hormones ethylene, jasmonate, and gibberellins. Also, spermidine and spermine were positively regulated with salicylic acid, auxin, and cytokinin signaling (Anwar et al., 2015). Metabolomic data obtained on these tomato fruits (engineered to have altered polyamine, ethylene, or methyl jasmonate levels) have paved the way for modulating tomato fruit attributes via a crosstalk between plant hormones ethylene/methyl jasmonate using sustainable cropping agroecosystems (Fatima et al., 2016).

Nitric oxide (NO) is another ubiquitous secondary messenger that, in response to environmental and endogenous cues, interacts with almost all plant hormones to varying degrees. NO is a negative regulator of ethylene (Manjunatha, Lokesh, & Neelwarne, 2010); in NO-fumigated tomatoes, ethylene production was inhibited, involving downregulation of transcription of ACC oxidase genes (ACO1, ACOH2, ACO4) (Aboul-Soud, 2010; Eum, Kim, Choi, & Lee, 2009). NO S-nitrosylates methionine adenosyl transferase and reduces the availability of methyl substrates for ethylene biosynthesis (Manjunatha, Gupta, Lokesh, Mur, & Neelwarne, 2012). In addition to the reduction in transcription of ACC oxidase genes, sodium nitroprusside released NO can delay tomato pericarp reddening and enhance activities of enzymes such as superoxide dismutase, catalase, and peroxidase (Lai, Wang, Li, Qin, & Tian, 2011). Overaccumulation of NO in short root (shr) tomato mutant delayed fruit ripening and led to enhancement in tyrosine, indole-3-acetic acid, and indole-3-butyric acid but a reduction in fatty acids and ABA content (Bodanapu et al., 2016). NO negates ethylene perception in shr mutant fruits (Bodanapu et al., 2016). More information is required on the role of NO in delaying the ripening and extending the shelf life of tomato fruits.

Building Nutrition and Flavor-Rich Tomato Fruit for Promoting Human Health

Epidemiological studies support the common contention that foods rich in phytonutrients help in the maintenance and promotion of human health and reduce disease risk of certain cancers as well as cardiovascular and chronic degenerative diseases (Virtanen, Voutilainen, Nurmi, Tuomainen, & Mursu, 2013; Yamada et al., 2011). Examples of such phytonutrients include vitamins (tocopherols, tocotrienols, ascorbic acid, and dehydroascorbic acid), carotenoids, phenolics/flavonoids, triterpenoids, and glucosinolates, many of which have antioxidative and free radical scavenging properties (Gerster, 1997; Kanellis & Manganaris, 2014; Liu, 2013). The phytonutrient-based protective capacity against or ability to delay the incidence of fatal diseases is thought to involve their antioxidative and free radical scavenging properties, which protect cellular macromolecules from oxidative damage (Mattoo, Minocha, et al., 2010). Because disease is associated with highly oxidative milieu, the dietary phytonutrients have the potential of protecting against disease(s) (García-Mier, Guevara-González, Mondragón-Olguín, Del Rocío Verduzco-Cuellar, & Torres-Pacheco, 2013). Among these, lycopene is a carotenoid that has been linked to reduced risk of various cancers including of the prostate, lung, stomach, pancreas, cervix, and colon as well as colorectal, oral, and esophageal cancers (Agarwal & Rao, 2000; Giovannucci, 1999). The antioxidant capacity of lycopene in vitro is higher than other carotenoids, β‎-carotene, and vitamin E. Other than its antioxidant and anticarcinogenic properties, lycopene is cardioprotective, anti-inflammatory, and antimutagenic in nature (Friedman, 2013). Other phytochemicals present in tomato include phytofluene, polyphenols, and flavonoids (quercetin and kaempferol). The phenolic acids (polyphenols) and flavonoids also have antioxidant properties and have been associated with reduced risk of age-related diseases, heart ailments, and cancers (Ross & Kasum, 2002).

Given that fruits such as tomato contain healthful nutrients, the reality is that the levels of these phytonutrients in most produce is, in fact, below the recommended daily allowance for maintaining human health. The traditional/conventional plant breeding process has not been able to increase the endogenous levels of such phytonutrients because the endogenous metabolic pathways involved are highly regulated. Moreover, it takes 10 to 15 years to release a new tomato variety. There is thus an important need to enhance the endogenous levels of phytonutrients in vegetables and fruits, including tomato. Employing genetic engineering to substantially enhance the levels of phytonutrients in fruits crops, including tomato, is a good avenue, since this path has shown the promise of building robust phytonutrient levels in crop plants, including tomato (reviewed in Mattoo, Shukla, Fatima, Handa, & Yachha, 2010; see also Kaur et al., 2017).

Nutritional Carotenoids

Considerable experimentation has gone into enabling genetic manipulation of carotenoid content and elevating nutritional quality of tomato fruit (d’Ambrosio et al., 2004; Fraser et al., 2002; Guo, Zhou, Zhang, Xu, & Deng, 2012; Mehta et al., 2002; Nambeesan et al., 2010; Neily et al., 2011; Rosati et al., 2000). Engineering the levels of higher polyamines, spermidine and spermine, specifically in tomato fruit resulted in two- to threefold enrichment (120–175 µg/g fresh weight) in lycopene compared to the control line as well as the micronutrient choline in addition to the attribute of higher processing quality (Mattoo et al., 2006; Mehta et al., 2002). Further, manipulation of a bacterial gene (phytoene synthase [crtB]) in tomato fruit increased phytoene (2.4-fold), lycopene (1.8-fold), β‎-carotene (2.2-fold), and lutein levels (Fraser et al., 2002). Likewise, expression of the citrus lycopene β‎-cyclase (crtl-b) in tomato led to a fourfold increase in β‎-carotene levels (Guo et al., 2012). RNAi repression resulted in altered accumulation of phytoene and lycopene. This led to a fourfold increase in lycopene and a ninefold increase in β‎-carotene in red fruits of transgenic tomato (Luo et al., 2013). These positive findings have generated a lot of interest in manipulating carotenoid levels in tomato and, in the process, have helped enhance understanding of the means plants employ to regulate endogenous gene expression. Thus it has also become apparent that the plant hormone ABA is a negative regulator (Galpaz, Wang, Menda, Zamir, & Hirschberg, 2008; Sun et al., 2012) and an ORANGE (OR) gene a positive regulator of carotenoid synthesis (Yazdani et al., 2019) in tomato.

Flavonoids and Ascorbate (Vitamin C) Antioxidants

Other antioxidants that modulate tomato fruit color, flavor, and texture are called phenolic acids and flavonoids. Tomato fruit flesh has more carotenoids than flavonoids, raising a need also to enhance flavonoid content by genetic engineering (since this technology is more robust than known thus far). The main tomato flavonoids are naringenin-chalcone and rutin (quercetin rutinoside), which accumulate in the peel. Tomato fruits were engineered to constitutively overexpress petunia chalcone isomerase (CHI) and as much as 78-fold more flavonols (quercetin glycoside, rutin) accumulated in the fruit peel (Muir et al., 2001). Tomato fruit is deficient in making resveratrol because it lacks the gene stilbene synthase (StSy). This deficiency was circumvented by engineering heterologous plant genes and expressing them in tomato. This strategy enabled enrichment of flavonoids (D’Introno et al., 2009; Giovinazzo et al., 2005; Schijlen et al., 2006), trans-resveratrol, and trans-glucopyranosides (piceid) (D’Introno et al., 2009; Giovinazzo et al., 2005; Schijlen et al., 2006) in transgenic tomato fruit. Likewise, a combined overexpression of two flavonoid biosynthesis pathway genes, chalcone synthase (CHS1) and chalcone reductase (CHR) from Petunia and Alfalfa, respectively, enabled a threefold higher levels of novel flavonoids, flavones, and flavonols (butein, isoliquiritigenin, naringenin, chalcone, and rutin in tomato (Schijlen et al., 2006). Apart from achieving higher levels of flavonoids (flavones and flavonols), the total antioxidant capacity of tomato fruit peel was increased approximately threefold (Schijlen et al., 2006).

Transcription factors are regulators of gene expression, and their use has enabled engineering the levels of many other health-promoting molecules. For instance, tomato fruit-specific enrichment with anthocyanins was achieved by expressing snap dragon transcription factors (Rosea1 [Ros1] and Delila [Del]) (Butelli et al., 2008). Property of anthocyanins lies in the protection against certain cancers, cardiovascular disease, and age-related degenerative diseases; in addition, anthocyanins are anti-inflammatory in nature and promote visual acuity as well as lessen the risk of obesity and diabetes. Transcriptional regulation of secondary metabolism was apparent from an earlier study in which maize transcription factors (MYB-type C1 and MYC-type LC) were used to transform tomato fruit for increasing the levels of higher flavonoids, mainly kaempferol content (Bovy et al., 2002). Notably, when Arabidopsis transcription factor AtMYB12 was employed to enhance the levels of flavonoids in tomato, it led to high amounts of chlorogenic acid (27-fold), dicaffeoyl quinic acid (26-fold), tricaffeoyl quinic acid (42-fold), quercetin rutinoside (67-fold), and kaempferol rutinoside (593-fold) in the transgenic tomato fruit (Luo et al., 2008). Following the same strategy, overexpression of a flavonoid-related R2R3-MYB transcription factor ANTHOCYANIN1 (ANT1) from wild tomato (Lycopersicon chilense) enhanced anthocyanadins, including petunidin, malvidin, and delphinidin in the fruit (Schreiber et al., 2012). The strength of AtMYB12 in enhancing the content of different flavonoids was followed by another study that utilized this transcription factor to augment levels of flavonols and hydroxycinnamates by 10% (100 mg per g DW) of fruit dry weight, likely via increased supply of carbon from primary metabolism to secondary metabolism (Zhang et al., 2015). This latter point is important because it is the secondary metabolism, dependent on carbon supply from primary metabolism, that is basically what leads to the synthesis of many nutritionally important biomolecules.

Ascorbic acid (vitamin C) is another essential nutrient in the human diet and commonly found in tomato and other fruits/vegetables (Mellidou & Kanellis, 2017). It is important for tissue repair, immune system function, formation of collagen, and generation of neurotransmitters. It is an antioxidant important for maintaining healthy skin, cartilage, teeth, bone, and blood vessels. A deficiency of ascorbic acid results in development of scurvy, a disorder causing muscular weakness, rash, and joint pain. Ascorbate-rich fruits including tomato are essential for human health. Improving vitamin C content in tomato fruit is becoming a desirable goal of breeding programs. According to various national agencies, the recommended dietary allowance of ascorbic acid has been set anywhere from 45 mg per day (World Health Organization) to as much as 110 mg per day (European Food Safety Authority). In tomato fruits, total ascorbic acid actually decreases as the fruit matures (Figure 5). Green tomato fruits contain a relatively higher amount of total ascorbic acid (23.4 mg per 100 g), but these levels decrease to 13.7 mg per 100 g in red ripe tomatoes (USDA, 2019). The wild progenitor Solanum pennellii of commercially cultivated tomato varieties (Solanum lycopersicum accessions) is much richer in ascorbic acid content (47.5 mg per 100 g) (Di Matteo et al., 2010), which means that ascorbic acid levels gradually declined with the advancement in selection and domestication of tomato genotypes. Ascorbic acid pool size is mainly governed by two critical enzymes. GDP-D-mannose-3,5-epimerase (GME) converts GDP-D-mannose into GDP-L-galactose (Bulley & Laing, 2016) whereas GDP-L-galactose phosphorylase (GGP) catalyzes the conversion of GDP-L-galactose to L-galactose-1-P (Mellidou & Kanellis, 2017). Expression studies have confirmed a positive correlation between transcript levels of genes encoding these enzymes with total ascorbic acid concentration during tomato fruit ripening (Ioannidi et al., 2009; Mellidou et al., 2012; Wang et al., 2013), suggesting a strong influence of GDP-D-mannose-3,5-epimerase and GDP-L-galactose phosphorylase on ascorbic acid biosynthesis.

Fruit Aroma and Flavor Volatiles

Volatile compounds contribute to aroma and flavor of the fruit (Baldwin, Kessler, & Halitschke, 2002). Major aromatic compounds include esters, ketones, terpenoids, lactone, aldehydes, and alcohols. In tomato, 20 to 30 aromatic volatiles are present in quantities sufficient enough to stimulate human olfactory system and establish tomato flavor (Klee & Giovannoni, 2011). Hexanal, Z-3-hexenal, E-2-hexenal, hexanol, and Z-3-hexenol are major volatile compounds derived from oxygenation of unsaturated fatty acids (Bai et al., 2011). Although extensive studies in the past have added a wealth of information about aromatic pathways in tomato fruit and the contribution of major volatile compounds, relatively little has been accomplished in the last decade. However, overexpression of aromatic L-amino acid decarboxylases (LeAADC1A and LeAADC2) in tomato led to a 10-fold increase in the emission of volatiles, 2-phenylacetaldehyde and 2-phenylethanol (Tieman et al., 2006). TomloxC is one of the tomato lipoxygenase family of genes (Upadhyay & Mattoo, 2018), which is involved in generating fatty acid-derived flavor components in tomato (Chen et al., 2004). Reduction in TomloxC transcripts via a transgenic strategy caused reduction in the flavor volatiles including hexenal, hexanal, and hexanol, data that helped to link this gene with the aroma/flavor attributes in tomato (Chen et al., 2004). An academic offshoot of experimenting to enhance fruit flavor and volatiles has been the discovery of rigid regulation of secondary metabolism in plants, including tomato. Thus an increase in phenylpropanoids was not followed by an increase in phenylalanine-derived flavor volatiles, suggesting the existence of other factors that limit synthesis of flavor volatiles even when the substrate is available (Cin et al., 2011). Tomato genotypes containing loci from wild species Solanum pennellii thereafter revealed that a complexed molecule, 4-coumarate:CoA, redirects the flux of phenylpropanoids toward biosynthesis of glycosides in tomato fruit (Rigano et al., 2016).

In the context of developing a flavorful tomato to meet the consumer demand for a tasty product, a major study has revealed that traits defining volatile molecules have been randomly lost due to domestication of tomato during breeding strategies for producing a large size tomato (Tieman et al., 2017). It is apparent that the transgenic approach to enhance the potential of edible produce is a valuable approach, particularly to enhance flavor and quality of tomato for human health. One consequence of engineering tomato fruit with a higher level of growth regulators such as spermidine and spermine has been significantly higher fructose/glucose and acid [citrate+malate]/sugar [glucose+fructose+sucrose] ratio in the engineered red fruits (Mattoo et al., 2006), an attribute considered as higher quality in tomato breeding programs. Other examples include enhancing the contents of vitamin C (Garchery & Gest, 2013; Garcia et al., 2009; Zhang et al., 2011) and folates (de la Garza et al., 2007; Waller et al., 2010).

Epigenetics: Additional Check Point for Improving Tomato Fruit

Epigenetics involves switching genes on or off via DNA methylation/demethylation process and regulates how cells regulate gene function without changing the DNA sequence. Thus, such combinatorial gene mapping can help to change a gene’s state and aid toward engineering plants by removing/silencing unwanted genes and keeping good ones intact and active. One can then develop new plants whose fruit such as tomato can acquire and maintain a high dose of nutrition, longer-lasting quality, and improved taste/flavor. Epigenetics can thus influence how cells produce relevant proteins, thereby it adds another layer over coordinated development programs, for example, fruit maturation and ripening (Farinati, Rasori, Varotto, & Bonghi, 2017). The role of DNA methylation in the regulation of fruit ripening in tomato has begun to emerge. During fruit development, DNA methyltransferase 1 (MET1), chromomethylases, and domains rearranged methyltransferases keep ripening genes methylated by adding a methyl group to carbon 5 of cytosine (5-methylctyosine: 5mC), thus silencing developmentally regulated CHROMOMETHYLASE3 (SlCMT3) reduced methylation at CHG sites in the promoter of SBP-box transcription factor COLOURLESS NON-RIPENING (CNR) and in the genomic regions associated with MADS-RIN binding sites (Chen et al., 2015). Promoters of ripening-related genes in ripening-impaired mutants (Cnr and rin) are consistently methylated as compared to a gradual decline of methylation levels observed in wild-type fruits (Zhong et al., 2013). When tomato plants were exposed to methyltransferase inhibitor 5-azacytidine, it causes demethylation of RIN-binding sites and results in premature ripening of fruit (Zhong et al., 2013). Eight genes putatively encoding 5mC methyltransferases and four DEMETER-LIKE DNA demethylases have been identified in tomato (Chen et al., 2015; Teyssier et al., 2008).

These demethylases remove the epi-marks leading to the ripening processes (Gallusci, Hodgman, Teyssier, & Seymour, 2016; Law & Jacobsen, 2010; Zhu, 2009). In tomato, RNAi-mediated suppression of SlDML2 resulted in hyper-methylation and transcriptional repression of RIN, NON-RIPENING (NOR), and carotenoid synthesis gene, PHYTOENE SYNTHASE 1 (PSY1) (Liu, How-Kit, et al., 2015). Reduction in the transcript levels of SlDML2 in the ripening mutants of tomato (Liu, How-Kit, et al., 2015), along with a strong expression of SlDML2 and SlDRM7 during early phases of fruit ripening (Liu, How-Kit, et al., 2015; Teyssier et al., 2008), are suggestive of the existence of a regulatory loop between DNA demethylation machinery and RIN, NOR, and CNR transcription factors during tomato fruit ripening (Gallusci et al., 2016; Liu, How-Kit, et al., 2015). Reciprocally, an interplay of methylome dynamics with similar transcription factor is also possible (Giovannoni et al., 2017).

SlDML2-mediated demethylation has been shown to induce transcription of genes involved in the synthesis and signaling of ethylene, production of pigments/flavor volatiles, and hydrolysis of cell wall (Lang et al., 2017), important information that can be applied to create a more flavorful tomato fruit. Although research on tomato has been focused on unraveling the influence of epi-mutations on major ripening regulators, the extent and role of epigenetic regulation of ripening, particularly in relation to improving nutrition and flavor, is begging for attention. Likewise, the roles of other genetic players such as histone modification, DNA methylation, chromatin remodeling, and microRNAs in the biosynthesis, regulation, conjugation, transport, and signal transduction of plant hormones in tomato are still poorly understood.

Tomatoes and the Environment

Environmental extremes such as drought, cold, heat, salinity, and other negative conditions impact plant growth, health, and productivity, and this is true for tomato plants as well. Much scientific effort has gone into understanding responses of plants to these stresses (Gerszberg & Hnatuszko-Konka, 2017). These approaches include engineering genes encoding functional and structural proteins, genes involved in regulatory and signaling pathways, transcription factors (Wang et al., 2015), and stress mitigating enzymes (Lim, Jeong, Jung, & Harn, 2016; Lyu et al., 2013; Vincour & Altman, 2005; Wang, Zhang, Liu, & Li, 2011) as well as higher expression of stress hormones and their receptors (Fabregas et al., 2018; Upadhyay & Mattoo, 2018). Thus a huge body of novel information has accumulated about different players that directly or indirectly impart tolerance to abiotic stresses. These include proteins such as dehydrins, heat shock proteins and late embryogenesis abundant proteins, osmolytes (trehalose and glycine betaine, signaling molecules) polyamines, and hormones (ABA, ethylene and methyl jasmonate) that have been validated (see Mattoo, 2014, and references therein). Also, genes that respond to stress have been identified by comparative transcriptomics. Those validated for more than a single abiotic stress are transcription factors b-ZIP, ERF/AP2 family, DOF, HD-ZIP, MYB, NAC, WRKY, and Zn-finger, which regulate endogenous processes in plants (reviewed in Shukla & Mattoo, 2013; see also Mattoo et al., 2014). Successful efforts on engineering tomato plants for resistance to different abiotic stresses have started paying off, as industry has already generated some drought-resistant germplasm for the farmers.

Trichomes, Herbivory, and Defense

To prevent plants from herbivores and mechanical wounding, tomato plants utilize trichomes, which abound epidermally on their leaves and stems (Huchelmann, Boutry, & Hachez, 2017; Shepherd & Wagner, 2007). Trichomes become a trap as well as a physical hindrance against the herbivory of leaves and stem by small insects (Lobato-Ortiz, Schuster, & Mutschler, 2007; Simmons, Gurr, McGrath, Martin, & Nicol, 2004). Seven types of trichomes are present in tomato plants, including glandular trichomes (types VI and VII), which comprise four- to eight-celled heads (Thipyapong, Joel, & Steffens, 1997). The shape of the head of type VI glandular trichomes differs in wild accessions and modern-day tomato cultivars (Bergau et al., 2015). Water-deficient conditions result in higher trichome density in tomato plants compared to well-watered conditions (Galdon-Armero et al., 2018). In addition to mitigating water stress conditions, the trichomes create hinderance for insect movement by producing sticky exudates, toxicants, and antinutritional proteins and repellents on aerial surfaces (Figure 6) (Frelichowski & Juvik, 2001; Lobato-Ortiz et al., 2007; Simmons et al., 2004; Thipyapong et al., 1997).

Figure 6. An illustration of defense mechanisms in tomato against insect or pathogen invasion. Various endogenous compounds (acyl sugars, α‎-tomatine, SAPs, SLs) are associated with defense response against pathogen infection. NBS-LRR proteins regulate signal transduction pathways leading to pest or disease resistance. microRNAs negatively regulate expression of NBS-LRRs whereas lncRNAs modulate effects of miRNAs. Proteinase inhibitors protect plant tissues from insect attack by inhibiting activity of proteases in insect guts. Upon recognition of pathogenic effector (Avr) proteins, plant resistance (R) proteins activate MAPKKKε‎ which activates a MEK2, SIPK, and WIPK cascade to establish hypersensitive response cell death. The miR164 post-transcriptionally regulates ORE1 which responds to senescence-inducing stimuli and triggers senescence process. Promotive or inhibitory effect is marked with arrow or bold-headed lines, respectively. Illustration is developed based on the information available in previous reports. Abbreviations: Avr, pathogenic effector protein; lncRNAs, long noncoding RNAs; MAPKs, mitogen-activated protein kinases; MEK2, MAP kinase kinase 2; miR, microRNA; NBS-LRRs, nucleotide-binding site leucine-rich repeat proteins; ORE1, NAC TF ORESARA1; R protein, plant resistance proteins; SAPs, stress-associated proteins; SIPK, salicylic acid-induced protein kinase; SLs, stringolactones; WIPK, wound-inducible protein kinase.

These trichomes also produce volatile monoterpenes α‎- and β‎-pinene, limonene, and cis-β‎-ocimene (Li et al., 2004), which attract natural enemies of herbivores (Buttery & Ling, 1993; Buttery, Ling, & Light, 1987). Also, rupture of foliar glandular trichomes releases hydrogen peroxide on leaf surfaces and induces the synthesis of the plant defense hormone jasmonic acid (Wasternack et al., 2006). Jasmonic acid promotes synthesis of trichome-derived terpenes (Chen, Klinkhamer, Escobar-Bravo, & Leiss, 2018); a tomato regulatory transcription factor SlMYC1 is essential for type VI glandular trichome development (Flood, 2019; Xu et al., 2018). Strategies to engineer tomato glandular trichomes are also underway to further study diversity in biosynthesis of specialized plant metabolites (Fan, Miller, Liu, Jones, & Last, 2017; Kortbeek et al., 2016; Schilmiller, Gilgallon, Ghosh, Jones, & Last, 2016).

Drought Stress Tolerance

Mannitol, a sugar alcohol synthesized from fructose, is an important osmolyte in plants. Introduction of its heterologous bacterial (Escherichia coli) mt1D gene in tomato plants led to the transgenic tomato being tolerant to abiotic stresses drought, cold, and salinity (Khare et al., 2010). A strategy that genetically transformed tomato plants with fused trehalose-6-phosphate synthase and trehalose-6-phosphate phosphatase genes also resulted in transgenic plants that had enhanced drought and salt stress tolerance (Lyu et al., 2013). Plants that can maintain the activity of vacuolar proton ATPase (V-ATPase) enzyme also have the ability to survive stress conditions—thus overexpression of an apple VHA-B (subunit of the V-ATPase) in tomato led to the accumulation of another stress fighter called proline, and the corresponding transgenic tomato was found to be drought tolerant (Hu et al., 2012). Transgenic tomato plants have been developed with tolerance to drought conditions via overexpression of the heterologous transcription factors Osmyb4 gene, encoding MYB (Vannini et al., 2007); DREB1A/CBF3 (Rai, Prakash Rai, Rathaur, Kumar, & Singh, 2013); and ZAT12 expressing a C2H2 zinc finger (Rai, Singh, & Shah, 2013). Dehydrins and late embryogenesis abundant proteins are other stress-relieving molecules that impart tolerance/adaptation to abiotic stressors. For example, transgenic tomato plants overexpressing the dehydrin tas14 gene were tolerant to long-term drought (and salinity) (Muñoz-Mayor et al., 2012), and cold-induced SK3-type (ShDHN) dehydrin (from wild tomato—Solanum habrochaites) enhanced tolerance to multiple abiotic stresses in tomato (Liu, Yu, et al., 2015). Constitutive overexpression of a polyamine synthesis gene, arginine decarboxylase PtADC (Poncirus trifoliate), in tomato plants imparted enhanced tolerance against drought stress and dehydration and also led to decreased accumulation of reactive oxygen species (ROS) (Wang et al., 2011).

Salt Stress Tolerance

Tomato is also sensitive to excessive salt (Foolad, 2007). Genes that impact salinity stress include ion transporters, scavengers of ROS, and osmotic homeostasis enablers (reviewed in Kaur et al., 2017). Glycine betaine is a quaternary ammonium compound that helps maintain osmotic potential: Overexpression of betaine aldehyde dehydrogenase gene maintained osmotic potential under salt stress in transgenic tomato (Jia, Zhu, Chang, & Li, 2002; Moghaieb et al., 2000). Genes regulating ion transporters are important in enhancing salt (and drought) tolerance in tomato. Overexpression of antiporter genes seems to have great potential in developing plants that can withstand salt stress. Recent examples can be found in Garcia-Abellan et al. (2014), Leidi et al. (2010), and Yarra et al. (2012). Other examples include overexpression of glyoxalase genes GlyI (glyoxalase I) and GlyII (glyoxalase II) (Álvarez-Viveros et al., 2013); overexpression of fatty acid desaturases, which convert 18:2 linoleic acid to 18:3 linolenic acid (Wang et al., 2014); and expression of D-galacturonic acid reductase gene (GalUR) (Lim et al., 2016). The latter transgenic lines were remarkable since they had an added dose of ascorbic acid and chlorophyll under salt stress.

Cold Stress Tolerance

Tomato suffers from chilling injury at temperatures below 13°C, causing substantial economic losses due to fruit quality deterioration, lesion development, loss of seed viability, and uneven ripening. Chilling temperatures alter physiology, metabolism, and macromolecular processes (reviewed in Miura & Furumoto, 2013). Attempts to contain chilling injury symptoms and develop cold resistance in tomato have had some success. Thus, tomato (cv. Moneymaker) transformed with a gene that catalyzed the conversion of choline to glycine betaine improved chilling stress tolerance of the transgenic plants (Park, Jenknic, Pino, Murata, & Chen, 2007). Genetically engineered tomato plants overexpressing LetAPX (tomato thylakoidal ascorbate peroxidase gene) were found tolerant to cold stress (Wang, Wisniewski, Meilan, Cui, & Fuchigami, 2006), but these changes were accompanied by reduction in chlorophyll, glutathione, and APX activities in comparison to the control plants (Duan, Feng, Wang, Li, & Meng, 2012). Polyamines are also called stress-imparting molecules and protect plants against different abiotic stresses (Mattoo, 2014; Mattoo, Upadhyay, & Rudrabhatla, 2015). Tomato fruit engineered for the ripening-associated accumulation of polyamines, spermidine and spermine, when exposed to 2°C chilling temperature, led to the accumulation of a pathogenesis-related protein (PR1b1), which remained abundant in rewarmed chilled fruit for an extended period compared to the control fruit deficient in these two polyamines (Goyal et al., 2016). A positive correlation was found between enhanced PR1b1 protein levels, gene transcripts (of MYC2, MYB1 and CBF1), and salicylic acid levels in the high spermidine/spermine transgenic tomato fruit (Goyal et al., 2016). It was proposed that polyamine-mediated accumulation of PR1b1 protein in rewarmed chilled tomato could be a preemptive plant defense mechanism related to cold stress-induced disease resistance phenomenon, the function and mechanisms of which are yet to be determined (Moyer, Londo, & Gadoury, 2015).

Heat Stress Tolerance and Heat Shock Proteins

A short heat (30º–50°C) treatment of tomato fruit delays fruit softening and increases storage/shelf life of tomatoes (Iwahashi & Hosoda, 2000; Mama, Yemer, & Woelore, 2016). During this response, more than 22% of pericarp proteins were lost, and a new group of proteins to the tune of 1.1% surfaced. These new proteins were identified as antioxidant enzymes, heat shock proteins, and cell-wall related proteins (Iwahashi & Hosoda, 2000). Tomato is known to accumulate heat shock proteins upon heat treatment/exposure. Heat shock protein accumulation seems also correlated with chilling tolerance of tomato (Sabahet, Weiss, & Lurie, 1996). Tomato harbors clusters of class-I small heat shock chaperone genes that are transiently regulated by ethylene and involve SlMADS-RIN transcription factor (Shukla et al., 2017). Another heat shock protein, tomato HSP21, was found to protect photosynthesis from temperature stress (Neta-Sharir et al., 2005). In accord with these discoveries, antisense-LeHSP100 transgenic tomatoes had reduced tolerance to heat stress suggesting that LeHSP100/ClpB contribute to the acquisition of thermotolerance (Yang et al., 2006). Tomato transformed with MasHSP24.4 (from wild banana) enabled the transgenic tomato to withstand a high temperature of 45°C (Mahesh et al., 2013).

Much new data has been unearthed through studies with transgenic tomatoes and new facets of tomato biology unveiled, which can be further utilized for improving the abiotic stress resistance in future cultivars.

Tomatoes and Disease

Biotic stress due to bacterial, insect, viral, or fungal infection/infestation poses a serious threat to crop yield and farm income. Over 40 bacterial and fungal pathogens are known to infect tomato crops (Khaliluev & Shpakovskii, 2013). Initial response of plant tissues to pathogens results in innate active or passive defense mechanism to counteract pathogen attack. Understanding pathogen diversification and evolution pattern has been helpful in the development of disease management strategies. With the start of 21st century, gene cloning and transgenic introduction of pathogen-resistant genes/loci via genetic engineering tools have led to the development of tomatoes resistant to specific pathogens (Bergougnoux, 2014; Khaliluev & Shpakovskii, 2013). Contemporary efforts are also in play to revolutionize conventional breeding programs with advanced biotechnological interventions. For example, Solanum sisymbriifolium is a wild relative of S. lycopersicum and has the potential to resist various pathogens that infect S. lycopersicum. Successful hybridization of S. lycopersicum with Solanum sisymbriifolium was achieved through in vivo crossing and embryo rescue techniques (Piosik, Ruta-Piosik, Zenkteler, & Zenkteler, 2019). Such efforts are further paving the way for breeding programs to introduce resistant genes from wild parents into domesticated genotypes. Similarly, incorporation of resistance (R) genes from wild tomato species Solanum pimpinellifolium or Solanum pennellii into cultivated tomato has also conferred resistance against Fusarium oxysporum f. sp. lycopersici (Catanzariti, Lim, & Jones, 2015, and references therein). Earlier reports have comprehensively elaborated the emerging research involving pathogen-plant interactions, components of pathogen resistance pathway, genes conferring resistance in plants against pathogens, and development of pathogen-resistant genotypes (Alkan & Fortes, 2015; Bergougnoux, 2014; Cui, Tsuda, & Parker, 2015; Fatima et al., 2008; Gaur, Verma, & Khurana, 2018; Karasov, Chae, Herman, & Bergelson, 2017; Mattoo & Handa, 2017; Parmar et al., 2017). This section focuses only on novel developments made in this aspect during last decade.

Insect Infestation

Insect attack on economically important crops causes severe losses in their potential yield. Insects, while causing damage to crops, also transmit viruses. For example, western flower thrips is a notorious carrier of Tomato Spotted Wilt Virus. Plant defense systems include proteinase inhibitors and secondary metabolites, which protect them from insect attack by inhibiting the activity of proteases in insect guts (Figure 2). Tomato plants overexpressing cysteine proteinase inhibitor (CeCPI) and a fungal chitinase (PjCHI-1) under pMSPOA promoter had detrimental effect on the growth of root-knot nematodes (Meloidogyne incognita) feeding on tomato plants (Chan et al., 2015).

Stringolactones are phytohormones derived from carotenoids. They positively regulate defense in tomato against root-knot nematodes (Xu et al., 2019). Also, basic helix-loop-helix (bHLH) transcription factor MYC2 negatively regulates nematode defense, possibly by mediating hormonal crosstalk among stringolactones, jasmonic acid, and abscisic acid (Xu et al., 2019). A comprehensive analysis of 16 genotypes revealed a high association of acyl sugar contents with plant resistance against two-spotted spider mite and whitefly (Maciel et al., 2018). Along similar lines, foliar metabolic profiling of tomato lines resistant or susceptible to feeding damage by western flower thrips revealed α‎-tomatine and a phenolic compound to be potential defensive compounds (Kim et al., 2019). During exploration of transgenic opportunities for pest resistance, constitutive overexpression of BtCry2A in tomatoes was found to develop complete resistance in plants against neonate larval instars of tomato fruit borer, Helicoverpa armigera (Hanur, Reddy, Arya, & Reddy, 2015).

Tomato roots constantly cooperate with beneficial microorganisms in the soil. Studies on the interactions between plant roots with beneficial rhizosphere microorganism Trichoderma hazianum showed that salicylic acid, ROS, jasmonic acid, and ethylene collectively limit fungal spread and regulate root growth in a step-wise process. After T. harzianum is recognized by tomato roots, salicylic acid and ROS are produced, which limit fungal infection whereas salicylic acid inhibits jasmonate and ethylene production, thereby controlling root colonization. Thereafter, ethylene and auxin induce root growth by stimulating nutrient transport and modifying root architecture (De Palma et al., 2019).

Fungal Pathogens

Fusarium oxysporum is a soil-borne fungal pathogen that colonizes in vascular tissues and causes wilting and death of plants, generally referred to as Fusarium wilt disease. In tomato plants, Fusarium oxysporum f. sp. lycopersici (Fol) releases specific effector (Avr) proteins into xylem sap. These disulfide-bonded proteins are recognized by the plant resistance (R) proteins and the plant defense response is activated. In tomato, three R proteins (I, I-2, I-3) are known to recognize their respective Avr proteins (Avr1, Avr2, Avr3) produced by Fusarium oxysporum f. sp. lycopersici (Houterman, Cornelissen, & Rep, 2008; Houterman et al., 2009; Rep et al., 2004) (Figure 6). Thus various classes of resistance R genes in complex effector-resistance protein interactions are involved in this resistance phenomenon (Catanzariti et al., 2015). Recent developments include the role of micro RNA in defense. Transcripts of two microRNAs, miR482f and miR5300, were found to be associated with susceptibility of tomato cultivars to Fusarium oxysporum f. sp. lycopersici (Ouyang et al., 2014). Mimic RNAs (of miR482/2118) enhance tomato resistance against infection with oomycete Phytophthora infestans and bacterial pathogen Pseudomonas syringae pv. Tomato DC3000 (Canto-Pastor et al., 2019). Also, tomato plants expressing a fungal gene (FvC5SD), which encodes iron-binding protein C-5 sterol desaturase in the ergosterol biosynthesis pathway, led to improved protection against Sclerotinia sclerotiorum due to deposition of their leaves with ~23% more epicuticular wax than control plants (Kamthan et al., 2012). These transgenic plants were found more resistant to drought, and fruits had enhanced content of iron and ω‎-3 and ω‎-6 polyunsaturated fatty acids (Kamthan et al., 2012). Among various exogenous application studies, NO increases tomato plant’s resistance against gray mold rot caused by Botrytis cinerea (Lai et al., 2011). Exogenous application of oxalic acid has been shown to induce resistance in tomato plants against Botrytis cinerea by increasing expression of oxalate oxidase and Germin in tomato (Sun et al., 2019). Interestingly, exogenous application of chitosan nanoparticles enhances biotic tolerance in tomato against Fusarium andiyazi, involving upregulation of superoxide dismutase gene and pathogenesis-related genes (PR-1, PR-2/β‎-1,3-glucanase, PR-8/chitinase, PR-10) (Chun & Chandrasekaran, 2019).

Bacterial Pathogens

Pseudomonas syringae pv. tomato causes bacterial spot disease in tomato. Transgenesis has the potential to develop resistance in tomato plants against such bacterial pathogens. Thus over- or misexpression of potato polyphenol oxidase (StPPO) in tomato led to reduction in incidence of Pseudomonas syringae pv. tomato infection (Li & Steffens, 2002; Thipyapong, Hunt, & Steffens, 2004). Similarly, transgenic overexpression of human cathelicidin antimicrobial peptide (hCAP18/LL-37) upregulated expression of pathogenesis-related protein (AT4G25780), bifunctional inhibitor/lipid transfer protein (AT5G38195), and cysteine-rich antifungal protein precursor (AT1G75830), which resulted in 15% growth inhibition of bacterial soft rot, caused by Pectobacterium carotovorum ssp. Carotovorum, and 35% growth inhibition of bacterial spot, caused by Xanthomonas campestris pv. Vesicatoria (Jung, 2013). Mitogen-activated protein (MAP) kinase cascade is associated with a signaling pathway related to plant immunity (Figure 6). A MAPKKK gene, SlMAPKKKε‎, has been identified to induce hypersensitive response cell death by activating a MAP kinase module and establish disease resistance in tomato plants against Xanthomonas campestris and Pseudomonas syringae strains (gram-negative bacterial pathogens) (Melech-Bonfil & Sessa, 2010).

Viral Pathogens

An efficient multiplex (RT-PCR) system to detect multiple viral diseases has been established. This system simultaneously detects Tobacco mosaic virus, Cucumber mosaic virus, Tomato Spotted Wilt Virus, Tomato chlorosis virus, Potato virus Y, and Potato virus X in tomato plants (Liu et al., 2019). Perturbations in transcript levels of some long noncoding RNAs have also been noticed in tomato plants infected with Tomato yellow leaf curl virus (Zhou et al., 2019).


World population is on the rise, as are concerns about production of enough food for the growing population. The educated consumer is concerned about food nutrition, and there is growing demand for health-enhancing fruits and vegetables. Major breakthroughs in sustainable agriculture, gene engineering technologies, and knowledge about nutritional enhancement of produce such as fruits and vegetables are valuable to develop new and valuable germplasm for human health purposes. Tomato is a common vegetable whose fruit has been engineered for higher levels and higher quality of nutrition-rich molecules, including carotenoids (lycopene in particular), vitamins including ascorbic acid, flavonoids, and polyphenols. Moreover, sustainable agricultural practices have been tested to determine the effect of varying agroecosystems on the quality of nonengineered and engineered tomato germplasm. Tomato is one of the major horticultural crops in regard to its consumption and its production volume in the world, cultivated on an area of ~4.8 million hectares with an annual production of 182 million tons. In addition to efforts to find mechanisms and processes to increase fruit yield and longer shelf life, the consumer’s recognition of fruits, including tomato fruit, as sources of health-promoting nutrients has intensified research on tomato. Excellent published research has unraveled dynamic physiological and biochemical changes during ripening of tomato while major advances have been made in the identification of gene regulators and hormonal crosstalk. The valuable information of players including transcription factors, microRNAs, signaling molecules, and their crosstalk at genetic and epigenetic levels is also being utilized toward understanding responses of tomato to vagaries of nature such as stresses due to cold and hot temperatures (both decrease the yield of tomatoes), drought, salinity, and herbivory. Thus genetic and biochemical determinants of pathways impacted by specific abiotic and biotic stressors are being unraveled that should help in developing new and engineered tomato plants that can withstand these stresses.


The review was prepared in the absence of any financial or commercial relationships that could be constructed as a potential conflict of interest. All authors equally contributed to writing, editing, commenting, revising and approving the manuscript. We acknowledge research work of all colleagues who have contributed to the understanding of fruit ripening and plant senescence. Due to a vast amount of literature in the subject matter, the authors apologize to those authors whose work was not included in this article. Autar K. Mattoo’s research is supported by United States Department of Agriculture.

Further Reading

  • Mattoo, A. K., & Handa, A. K. (Eds.). (2017). Achieving sustainable cultivation of tomatoes. Cambridge, U.K.: Burleigh Dodds Science Publishing.
  • Nath, N., Bouzayen, M., Mattoo, A. K., & Pech, J.-C. (Eds.). (2014). Fruit ripening: Physiology, signalling and genomics. Oxfordshire, U.K.: CABI.
  • Paliyath, G., Subramanian, J., Lim, L.-T., Subramanian, K. S., Handa, A. K., & Mattoo, A. K. (Eds.). (2019). Postharvest biology and nanotechnology. New York, NY: John Wiley.


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