Tomato Fruit Development and Metabolism

Tomato Fruit Development and Metabolism Muriel Quinet 1 * , Trinidad Angosto 2 , Fernando J. Yuste-Lisbona 2 , Rémi Blanchard-Gros 1 , Servane Bigot 1 , Juan-Pablo Martinez 3 and Stanley Lutts 1 1 Groupe de Recherche en Physiologie Végétale, Earth and Life Institute, Université Catholique de Louvain, Louvain-la-Neuve, Belgium, 2 Centro de Investigación en Biotecnología Agroalimentaria (BITAL), Universidad de Almería, Almería, Spain, 3 Instituto de Investigaciones Agropecuarias (INIA-La Cruz), La Cruz, Chile Tomato (Solanum lycopersicum L.) belongs to the Solanaceae family and is the second most important fruit or vegetable crop next to potato (Solanum tuberosum L.). It is cultivated for fresh fruit and processed products. Tomatoes contain many healthpromoting compounds including vitamins, carotenoids, and phenolic compounds. In addition to its economic and nutritional importance, tomatoes have become the model for the study of fleshy fruit development. Tomato is a climacteric fruit and dramatic metabolic changes occur during its fruit development. In this review, we provide an overview of our current understanding of tomato fruit metabolism. We begin by detailing the genetic and hormonal control of fruit development and ripening, after which we document the primary metabolism of tomato fruits, with a special focus on sugar, organic acid, and amino acid metabolism. Links between primary and secondary metabolic pathways are further highlighted by the importance of pigments, flavonoids, and volatiles for tomato fruit quality. Finally, as tomato plants are sensitive to several abiotic stresses, we briefly summarize the effects of adverse environmental conditions on tomato fruit metabolism and quality. Keywords: abiotic stress, fruit set, fruit ripening, genetic control, hormonal control, primary metabolism, secondary metabolism, Solanum lycopersicum INTRODUCTION Tomato (Solanum lycopersicum L.) is the second most important fruit or vegetable crop next to potato (Solanum tuberosum L.), with approximately 182.3 million tons of tomato fruits produced on 4.85 million ha each year (FAOSTAT, 2019). Asia accounts for 61.1% of global tomato production, while Europe, America, and Africa produced 13.5%, 13.4%, and 11.8% of the total tomato yield, respectively. Tomato yields are highly variable, ranging from more than 508 tons per ha in the Netherlands to fewer than 1.5 tons per ha in Somalia in 2017 (FAOSTAT, 2019), with an average global yield of 376 tons per ha. Tomato consumption is concentrated in China, India, North Africa, the Middle East, the US, and Brazil with tomato consumption per capita, ranging from 61.9 to 198.9 kg per capita (FAOSTAT, 2019). Tomato is a member of the Solanaceae family, which includes several other economically important crops such as potato, pepper (Capsicum annuum L.), and eggplant (Solanum melongena L.), representing one of the most valuable plant families for vegetable and fruit crops. Frontiers in Plant Science | www.frontiersin.org November 2019 | Volume 10 | Article 15541 Edited by: Robert Peter Walker, University of Perugia, Italy Reviewed by: Paolo Pesaresi, University of Milan, Italy Giuseppe Colla, Università degli Studi della Tuscia, Italy *Correspondence: Muriel Quinet [email protected] Specialty section: This article was submitted to Plant Metabolism and Chemodiversity, a section of the journal Frontiers in Plant Science Received: 31 May 2019 Accepted: 07 November 2019 Published: 29 November 2019 Citation: Quinet M, Angosto T, Yuste-Lisbona FJ, Blanchard-Gros R, Bigot S, Martinez J-P and Lutt S (2019) Tomato Fruit Development and Metabolism. Front. Plant Sci. 10:1554. doi: 10.3389/fpls.2019.01554 REVIEW published: 29 November 2019 doi: 10.3389/fpls.2019.01554 Tomatoes contain many health-promoting compounds and are easily integrated as a nutritious part of a balanced diet (Martí et al., 2016). In addition to consuming the fresh fruits, consumers use tomatoes in processed products such as soups, juices, and sauces (Krauss et al., 2006;Li et al., 2018b). Over the last decade, consumers have become more aware of foods as a source of health benefits and their roles in prevention of several chronic diseases and dysfunctions (Pem and Jeewon, 2015). Although a wealth of functional foodstuffs have been created to fulfil these requirements, it is important to note that the consumption of “conventional foods”such as fruits and vegetables is more effective for this purpose (Viuda-Martos et al., 2014). The nutritional importance of tomatoes is largely explained by their various health-promoting compounds, including vitamins, carotenoids, and phenolic compounds (Raiola et al., 2014;Liu et al., 2016;Martí et al., 2016;Li et al., 2018b). These bioactive compounds have a wide range of physiological properties, including antiinflammatory, anti-allergenic, antimicrobial, vasodilatory, antithrombotic, cardio-protective, and antioxidant effects (Raiola et al., 2014). Tomatoes are rich in carotenoids, representing the main source of lycopene in the human diet (Viuda-Martos et al., 2014). Carotenoids and polyphenolic compounds contribute to the nutritional value of tomatoes and improve their functional attributes and sensory qualities, including taste, aroma, and texture (Raiola et al., 2014;Tohge and Fernie, 2015;Martí et al., 2016). Tomatoesalso havethenaturallyoccurringantioxidants Vitamins CandE (Agarwal and Rao, 2000;Martí et al., 2016)aswellaslargeamountsof metabolites, such as sucrose, hexoses, citrate, malate, and ascorbic acid (Li et al., 2018b). Tomato fruit quality and metabolite biosynthesis are affected by plant growing conditions (Diouf et al., 2018). Tomato production is challenged by several problems around the world, including the scarcity of water resources, soil salinization, and other abiotic stresses (Fahad et al., 2017;Gharbi et al., 2017;Zhou et al., 2019). In particular, in countries with a Mediterranean climate, including some regions in southern Europe and North and South America, tomato cultivation is increasingly confronted with limiting conditions such as drought and salinity, which ultimately reduce the competitiveness of tomato farmers in these areas. This, in turn, impacts the integrity of the ecosystem, contributing to the relocation (abandonment) of rural sectors. In addition to its economic and nutritional importance, tomatoes have become the model for the study of fleshy fruit development(Karlovaetal.,2014;Kim etal.,2018;Lietal.,2018b). The entire tomato genome has been sequenced, serving as a rich genomic resource, and both genetic and physical maps and molecular markers are available for this species (The Tomato Genome Consortium, 2012;Suresh et al., 2014;Zhao et al., 2019). Moreover, a range of well-characterized monogenic mutants, TILLING populations, wild tomato species, recombinant inbred lines and genome editing tools are available (Eshed and Zamir, 1994;Minoia et al., 2010;Pérez-Martín et al., 2017;Li et al., 2018b; Martín-Pizarro and Posé, 2018;Tomato Genetics Resource Center, 2019;Rothan et al., 2019). Several databases contain gene expression analysis data (Fei et al., 2006;Suresh et al., 2014;Zouine et al., 2017;Shinozaki et al., 2018b), while recent progress in tomato metabolomics has provided substantial information about the primary and specialized metabolism of this species and the pathways involved in molecular biosynthesis and turnover (Luo, 2015;Tieman et al., 2017;Zhu et al., 2018). Dramatic metabolic changes occur during tomato fruit development (Carrari and Fernie, 2006). Tomato is a climacteric fruit, meaning it undergoes a surge in respiration and ethylene production at the onset of ripening (Li et al., 2019a). As ripening progresses, tomato fruits transit from partially photosynthetic to true heterotrophic tissues through the parallel differentiation of chloroplasts into chromoplasts and the dominance of carotenoids and lycopene in the cells of the ripe fruits (Carrari and Fernie, 2006). The ripening process has evolved to make fruit palatable to the organisms that consume them and disperse their seeds. In doing so, ripening activates pathways that generally influence the levels of pigments, sugars, acids, and aroma-associated volatiles to make the fruit more appealing, while simultaneously promoting tissue softening and degradation to permit easier seed release (Matas et al., 2009). In this review, we provide an overview of our current understanding of tomato fruit metabolism. We begin by detailing the genetic and hormonal control of fruit development andripening,afterwhichwedocumenttheprimary metabolismof tomato fruits, with a special focus on sugar, organic acid, and amino acid metabolism. Links between primary and secondary metabolic pathways are further highlighted by the importance of pigments, flavonoids, and volatiles for tomato fruit quality. Finally, as tomato plants are sensitive to several abiotic stresses, we briefly summarize the effects of adverse environmental conditions on tomato fruit metabolism and quality. GENETIC REGULATION OF THE DEVELOPMENT AND RIPENING OF TOMATO FRUIT Fruit Set and Early Fruit Development The genetic regulation of fruit development begins in the floral meristem (FM), where the architecture and organization of this tissue is determined, and continues until the later developmental stages before fruit ripening (Gillaspy et al., 1993)(Figures 1A,B). At the initial stage of tomato fruit development, the CLAVATAWUSCHEL (CLV-WUS) feedback loop controls meristem activity and regulates FM size, which in turn determines the final number of carpels in flowers and, hence, seed locules in fruits (Rodríguez-Leal et al., 2017). The signaling peptide CLV3 directly interacts with leucine-rich repeat receptor kinases, such as CLV1 or CLV2, to activate a signaling cascade that negatively regulates the stem cell-promoting transcription factor WUS (Somssich et al., 2016). Loss-of-function mutations in any of the CLV genes will therefore cause stem cell over proliferation, resulting in the development of extra floral organs and larger fruits (Xu et al., 2015;Rodríguez-Leal et al., 2017); for example, the joint action of the natural mutations fasciated (fas)andlocule number (lc) gave rise to large-fruited cultivars, in contrast to the Quinet et al. Tomato Fruit Metabolism Frontiers in Plant Science | www.frontiersin.org November 2019 | Volume 10 | Article 15542 bilocular fruits of tomato wild species and most small-fruited varieties (Tanksley, 2004;Barrero et al., 2006). The fas mutation is a 294-kb inversion disrupting the tomato CLV3 (SlCLV3)promoter (Xu et al., 2015), whereas lc is associated with two single-nucleotide polymorphisms in a putative CArG box regulatory element downstream of WUS (SlWUS)(Muños et al., 2011;van der Knaap et al., 2014).Furthermore,usingforwardgeneticsandCRISPR/Cas9 genome editing technology, Xu et al. (2015) identified the arabinosyltransferase genes FASCIATED INFLORESCENCE (FIN), FASCIATED AND BRANCHED2 (FAB2), and REDUCED RESIDUAL ARABINOSE 3a (RRA3a) as new components of the CLV-WUS pathway. The SlCLV3 peptide must therefore be fully arabinosylated to maintain meristem size since the loss of an arabinosyltransferase cascade causes floral and fruit fasciation. As the flower develops, the gynoecium is initiated in the fourth whorltoterminateFMactivity.TheMADSboxtranscriptionfactor AGAMOUS (AG) is required to form the carpel primordium (Yanofsky et al., 1990). Consequently, the downregulation of TOMATO AGAMOUS1 (TAG1), the tomato ortholog of Arabidopsis thaliana AG, gives rise to alterations in carpel development and determinacy by producing fruits that continue todevelopinanindeterminatefashion(Pnuelietal.,1994;Panetal., 2010;Gimenez et al., 2016). Furthermore, in Arabidopsis,AG turns off the stem cell maintenance program through the transcriptional repression of WUS via two different pathways: directly, by promoting the recruitment of Polycomb Group (PcG) proteins to methylate histone H3K27 at the WUS locus (Liu et al., 2011); and indirectly, by inducing the expression of a gene encoding the C2H2 zinc-finger protein KNUCKLES (KNU) (Sun et al., 2009). The inductionofKNU expression by AG requires a time delay regulated by the epigenetic modification of histones at the KNU locus (Sun et al., 2014). Recently, Bollier et al. (2018) demonstrated that the AGKNU-WUS pathway is conserved in Arabidopsis and tomato and regulates the timed termination of floral stem cell activity. In this context, the tomato mini zinc-finger protein INHIBITOR OF MERISTEM ACTIVITY (SlIMA) recruits SlKNU to form a transcriptional repressor complex together with TOPLESS and HISTONE DEACETYLASE19, which binds to the SlWUS locus to repress its transcription (Bollier et al., 2018). Additionally, it has been hypothesized that lc is a weak gain-of-function mutation that reduces or blocks the binding of TAG1 to the SlWUS 3′regulatory region, which impairs the ability of TAG1 to repress SlWUS, resulting in the formation of larger fruits as a consequence of the development of extra carpels (van der Knaap et al., 2014). The variation in tomato fruit morphology not only depends on CLV-WUS signaling pathway-related genes, but also on OVATE and SUN, which have a large effect on fruit shape (Figure 1B). The ovate null mutation gives rise to changes in cell division patterns during the earliest stages of gynoecium development, with more cells produced in the proximo-distal direction and fewer in the medio-lateral FIGURE 1 | Genetic and hormonal control of tomato fruit development. (A) Main stages of tomato fruit development. (B) Genes involved in the control of tomato fruit development that are mentioned in this article. (C) Main hormones involved in tomato fruit development during fruit set and fruit growth (green) and fruit ripening (red). (D) Genes involved in the hormonal regulation of fruit development that are mentioned in this article. The Figure summarizes data collected by Gillaspy et al. (1993);Srivastava and Handa (2005);Karlova et al. (2014) and Obroucheva (2014). Quinet et al. Tomato Fruit Metabolism Frontiers in Plant Science | www.frontiersin.org November 2019 | Volume 10 | Article 15543 direction,causingthedevelopmentofelongatedfruits(Kuetal.,1999; Liu et al., 2002;Rodríguez et al., 2011). In contrast, the effect of SUN on fruit shape is most noticeable at flower anthesis, when it begins to increasecelldivisionalongtheproximo-distalaxisandcellelongation immediately after fertilization (Xiao et al., 2009;Wu et al., 2011;van der Knaap et al., 2014). Thus, a profound shift in the expression of genes involved in cell division, cell wall development, and patterning processes was observed in the elongating fruit tissues of the sun mutant (Clevenger et al., 2015). Moreover, the MADS box gene ENHANCER OF J2 (EJ2) also seems to be involved in determining fruit shape; ej2 knockout mutants develop slightly elongated fruits together with several pleiotropic effects, such as branched inflorescences and jointless pedicels (Soyk et al., 2017). Amongthefruitweightregulators,CELL NUMBER REGULATOR (CNR)wasfoundtounderliethefw2.2 quantitative trait locus (QTL), acting early during the development of the gynoecium to increase ovary size (Frary et al., 2000;Guo and Simmons, 2011) and enlarge the placenta and columella fruit tissues (Cong et al., 2002;Gonzalo et al., 2009). SlKLUH is the causal gene for the fw3.2 QTL and encodes a CYP450 of the 78A class (Chakrabarti et al., 2013). One singlenucleotide polymorphism in the SlKLUH promoter leads to its enhanced expression in meristems and young flower bud tissues; however, the increased fruit weight of these mutant plants becomes evident only after fertilization. An increased number of cell layers in the pericarp gives rise to heavier fruits with a ripening delay, which has been hypothesized to be the result of the extension of the cell proliferation stage (Chakrabarti et al., 2013). Studies in Arabidopsis have suggested that KLUH is involved in generating a mobile growth-promoting signal, although its exact molecular and biochemical nature is yet to be deciphered (Anastasiou et al., 2007;Adamski et al., 2009). Cell expansion in the pericarp is responsible for the dramatic increase in fruit size from a 1to 2-mm gynoecium to a 5to 10-cm tomato fruit (Gillaspy et al., 1993;Xiao et al., 2009). The CELL SIZE REGULATOR (CSR) gene controls pericarp cell size and underlies the fw11.3 QTL (Huang and van der Knaap, 2011;Mu et al., 2017). CSR expression is restricted to fruits, starting about 5 days after pollination and decreasing at the onset of ripening. Along with the increased cell size, coexpression studies suggest that CSR is also involved in shoot development and phloem/xylem histogenesis; however, the molecular function of CSR in controlling these developmental processes remains unclear (Mu et al., 2017). Fruit Ripening At the end offruit development, when seeds are mature and ready for dispersal, tomato fruits undergo ripening, a complex developmental program involving the coordinated regulation of numerous physiological and biochemical changes that determine flavor, color, texture, and aroma. These changes involve the upor downregulation of numerous genes in various metabolic pathways (Alba et al., 2005;Fujisawa et al., 2011;Osorio et al., 2011). Multiple studies of the development and maturation of tomato fruits have facilitated the identification of specific genes that participate in ripening (Vrebalov et al., 2002;Manning et al., 2006;Giovannoni, 2007;Wang et al., 2009;Chung et al., 2010;Nashilevitz et al., 2010; Karlova et al., 2011;Pesaresi et al., 2014)(Figure 1B). Tomatoes are classified as climacteric fruits, exhibiting a peak of respiration and ethylene production at the start of ripening (Alexander and Grierson, 2002). The biosynthesis and perception of ethylene are highly regulated, involving genes conserved in various plant taxa (Seymour et al., 2013). Some transcription factors modulate ethylene biosynthesis and signal transduction during fruit ripening, among which it is worth highlighting RIPENING INHIBITOR (RIN) (Vrebalov et al., 2002), COLORLESS NON-RIPENING (CNR) (Manning et al., 2006), and NON-RIPENING (NOR) (Yuan et al., 2016). RIN acts as the main regulator offruit ripening, directly controlling the expression of target genes involved in a wide range of ripening-related events (Fujisawa et al., 2011;Qin et al., 2012). RIN encodes a SEPALLATA (SEP)-class MADS-box transcription factor (Vrebalov et al., 2002), which was previously considered to be an essential regulator of the induction of ripening (Vrebalov et al., 2002); however, its role in fruit ripening was recently reassessed following the publication of studies showing that RIN, although necessary to complete ripening, is not required for the initiation of this process (Ito et al., 2017). The rin mutant was found to be caused by the deletion of a genomic DNA fragment between RIN and MACROCALYX (MC), forming the chimeric gene RIN-MC (Vrebalov et al., 2002). MC affects inflorescence determinacy and sepal development (Vrebalov et al., 2002), and the rin mutant was found to be a gain-of-function mutant that produced a protein that actively represses ripening (Ito et al., 2008;Li et al., 2018a). RIN binds to the demethylated promoter regions of several genes, such as the ethylene biosynthesis genes SlACS2 (1-AMINOCYCLOPROPANE-1CARBOXYLIC ACID SYNTHASE 2), SlACS4,SlACO1 (ACC OXIDASE 1), the ethylene receptor NEVER RIPE (NR), and others whose products are involved in fruit softening and the transcriptional regulation of cell wall hydrolases [POLYGALACTURONASE (PG), b-GALACTOSIDASE4 (TBG4), ENDO-(1,4)-b-MANNANASE4 (MAN4), and a-EXPANSIN1 (EXP1)] (Klee and Tieman, 2002;Ito et al., 2008;Fujisawa et al., 2011;Martel et al., 2011;Shima et al., 2013;Ito et al., 2017). RIN also positively stimulates the expression of CNR (Cardon etal.,1999;Manning et al., 2006). The cnr mutationis the result ofa spontaneous epigenetic change that increases cytosine methylation in the promoter of a SQUAMOSA promoter-binding proteinencoding gene, which strongly decreases gene expression and produces colorless fruits with an altered pericarp texture (Manning et al., 2006). During ripening, the CNR promoter is progressively demethylated, but in cnr mutants, the promoter remains hypermethylated, preventing RIN from binding to it (Zhong et al., 2013). In addition, CNR was involved in the positive regulation of many ripening-related genes, including PG, PECTINESTERASE (PE), XYLOGLUCAN ENDOTRANSGLYCOSYLASE (XET), PHYTOENE SYNTHASE1 (PSY1), LIPOXYGENASE (LOX), and ACO1 (Eriksson et al., 2004). The nor mutant exhibits abnormal ripening as a result of a 2bp deletion in the NOR coding sequence, leading to the early termination of protein translation (Tigchelaar et al., 1973;Martel et al., 2011;Osorio et al., 2011). NOR encodes a NAC family Quinet et al. Tomato Fruit Metabolism Frontiers in Plant Science | www.frontiersin.org November 2019 | Volume 10 | Article 15544 transcription factor that regulates fruit ripening through a currently unclear mechanism, while mutations in this gene inhibit multiple metabolic processes and prolong fruit shelf life (Kumar et al., 2018). A study of the role of NOR and RIN in tomato fruit ripening confirmed that the nor mutation had a more global effect on ethylene/ripening-related gene expression than rin, suggesting that NOR might even act upstream of RIN in the transcriptional network controlling tomato fruit ripening (Osorio et al., 2011). In addition to NOR, three other NAC family genes, SlNAC1,SlNAC4,andNOR-like1,areknowntobe involved in the regulation of tomato fruit ripening (Ma et al., 2014;Zhu et al., 2014;Meng et al., 2016). Other ripening factors, such as the MADS box TOMATO AGAMOUS-LIKE1 (TAGL1) (Vrebalov et al., 2002;Giménez et al., 2010), tomato APETALA2 (SlAP2a) (Karlova et al., 2011), and the tomato homeodomain leucine zipper homeobox protein SlHB1 (Lin et al., 2008), exercise their regulatory functions by interactingwithRIN(Fujisawaetal.,2011;Qinetal.,2012;Seymour et al., 2013). TAGL1 (also referred to as ARLEQUIN in some publications), a PLENA lineage gene orthologous to Arabidopsis SHATTERPROOF1/2, controls many aspects of tomato fruit ripening (Vrebalov et al., 2009;Garceau et al., 2017), including the direct activation of the expression of the ethylene biosynthesis gene ACS2 (Itkin et al., 2009). Tomato fruits produced by TAGL1silenced plants had defects in ripening without their floral organ specification being affected (Vrebalov et al., 2009;Giménez et al., 2010;Pan et al., 2010). Plants with reduced TAGL1 expression produced fruits with a narrow pericarp and reduced firmness at the breaker stage, which remained yellow and produced significantly less ethylene than the control fruits (Vrebalov et al., 2009). The MADS box proteins TAGL1 and two homologs of FRUITFULL (FUL1/TDR4 and FUL2/MBP7) function as coregulators of RIN (Leseberg et al., 2008;Itkin et al., 2009;Vrebalov et al., 2009; Giménez et al., 2010;Martel et al., 2011;Bemer et al., 2012;Shima et al., 2013;Wang et al., 2014). Fujisawa et al. (2014) demonstrated that RIN, TAGL1, and the FUL homologs form a DNA-binding complex, probably a tetramer, which is believed to regulate tomato fruit ripening. The RIN and CNR regulators have been shown to function upstream of SlAP2a and to positively regulate its expression (Karlovaetal.,2014),whereasSlHB1controlsethylenemetabolismby binding to the regulatory regions of ACO1 (Lin et al., 2008). On the other hand, transcriptomic studies have shown that SlAP2a participates in the control of fruit ripening as a negative regulator of several processes involved in ethylene biosynthesis, and signaling pathways, as well as in the differentiation of chromoplasts (Chung et al., 2010;Karlova et al., 2011). HORMONAL REGULATION OF THE DEVELOPMENT AND RIPENING OF TOMATO FRUIT Fruit Set and Early Fruit Development Fruit set and fruit development are complex processes that require the coordination of different phytohormones (McAtee et al., 2013; Shinozaki et al., 2018b;Li et al., 2019b)(Figures 1C, D). From flower initiation to fertilization, the morphogenesis and growth of carpels and ovules require the spatial and temporal biosynthesis and action of auxins, cytokinins (CKs), and gibberellins (GAs) (Azzi et al., 2015). Shortly before anthesis, when the ovary has reached its mature size, abscisic acid (ABA) and ethylene work to stop growth within the ovary to maintain a temporally protected and dormant state (Gillaspy et al., 1993;Azzi et al., 2015). After the successful pollination and fertilization of the ovules, ovary growth resumes and the fruit and seeds develop concomitantly (Azzi et al., 2015). These changes are associated with a decrease in ABA and ethyleneconcentrationsandanincreaseinauxin,GAs,andCKs(de Jongetal.,2009;McAteeetal.,2013;Shinozakietal.,2015;Shinozaki et al., 2018a). GAs produced by pollen may increase auxin production in the ovary, which in turn may act as a signal for fruit set and the subsequent activation of cell division (Gillaspy et al., 1993;de Jong et al., 2009). Active fruit growth involving pericarp cell division and elongation is promoted by the biosynthesis of auxin in the developing seeds and GAs in the pericarp (Obroucheva, 2014). Auxins and GAs appear to be the predominant hormones required for tomato fruit initiation in response to fertilization, since the exogenous application of both hormones leads to fruit initiation andparthenocarpicdevelopment(deJong etal.,2009).CKs, ethylene, ABA, brassinosteroids, and polyamines (PAs) have also been shown to play a role in fruit formation, but this is currently less well documented (Srivastava and Handa, 2005;McAtee et al., 2013; Azzi et al., 2015;Shinozaki et al., 2015;Liu et al., 2018;Shinozaki et al., 2018a). In tomato, early fruit developmentis governed by theallocation of auxin to tissues and cells, which initiates signal transduction pathways(Azzietal.,2015).The PIN-FORMED(PIN)auxinefflux transport proteins were shown to be involved in fruit set and early tomato fruit development (Mounet et al., 2012;Pattison and Catalá, 2012). Silencing SlPIN4 resulted in the production of small parthenocarpic fruits exhibiting precocious development (Mounet et al., 2012). The auxin signaling pathway involves an auxin receptor called TRANSPORT INHIBITOR RESPONSE1 (TIR1) (Azzi et al., 2015). In the presence of auxin, TIR1 recruits the transcriptional repressors AUXIN/INDOLE-3-ACETIC ACID (Aux/IAA) and triggers their degradation by the 26S proteasome (Azzi et al., 2015), releasing the Aux/IAA-bound auxin response factors (ARFs) and initiating the auxin response through auxinresponsive element-mediated genetranscription(Azziet al.,2015). In tomato, the misexpression of TIR1 and specific members of the Aux/IAA and ARF gene family alters the normal flower-to-fruit transition and results in parthenocarpic fruit production (de Jong et al., 2009;Ren et al., 2011;Mounet et al., 2012;Azzi et al., 2015). However,Aux/IAA andARFgenesmayhaveopposingfunctionsto TIR regarding fruit set; the transcript abundance of SlIAA9 and SlARF7 decreased in SlTIR1-overexpressing plants, which resulted in the formation of seedless fruit (Ren and Wang, 2016;GoldentalCohen et al., 2017). The silencing of the Aux/IAA transcriptional repressor SlIAA17 resulted in larger fruits with thicker pericarp tissues, a phenotype caused by enhanced cell expansion (Su et al., 2014). Ren and Wang (2016) showed that SlTIR was regulated by GAs, auxins, ABA, and ethylene, suggesting that TIR may be a key Quinet et al. Tomato Fruit Metabolism Frontiers in Plant Science | www.frontiersin.org November 2019 | Volume 10 | Article 15545 mediatorofthecrosstalkbetweenauxinandotherphytohormones. The SlARF7/SllAA9 complex also mediates crosstalk between auxin and GA pathways to regulate fruit initiation through their interaction with the GA-signaling repressor SlDELLA (Hu et al., 2018). SlARF7/SllAA9 complex and SlDELLA antagonistically regulate genes involved in auxin and GA metabolism while they additively coregulate genes involved in fruit growth (Hu et al., 2018). Indeed, auxins do not act alone to trigger fruit development and fruit set; these processes are partly mediated by GAs, as part of a complex hormonal cross-talk with auxin (de Jong et al., 2009; McAtee et al., 2013;Azzi et al., 2015). Pollination triggers the upregulation of transcripts encoding GA 20-oxidases (GA20ox), which biosynthesize active GA1 and GA4 (Azzi et al., 2015). It was suggested that the expression of more than one GA20ox gene is required to control fruit set in tomato because the silencing of individual GA20ox genes did not strongly affect fruit set or development (Xiao et al., 2006;Olimpieri et al., 2011;Azzi et al., 2015). Despite this, the heterologous overexpression of citrus CgGA20ox1 in tomato resulted in an elevated GA4 content and parthenocarpic fruit development, demonstrating the influence of GA and GA20ox activity on fruit set and development (García-Hurtado et al., 2012). The GA signal transduction pathway requires the recognition of GA by its receptor, GA INSENSITIVE DWARF1 (GID1) (Azzi et al., 2015). The GID1-GA complex interacts with the nuclear repressor DELLA to target it for ubiquitin-dependent proteolytic degradation by the 26S proteasome (Azzi et al., 2015). This removes the repression of the GA-responsive genes, which are then able to initiate GA signal transduction. Consistent with this, the silencing of the SlDELLA gene in tomato resulted in small, facultative parthenocarpic fruits with an elongated shape (Martí et al., 2007). The procera (pro) mutant, which carries a point mutation in the GRAS region of SlDELLA, has also very strong parthenocarpic capacity and shows enhanced growth of preanthesis ovaries (Jones, 1987;Carrera et al., 2012;Shinozaki et al., 2018c). The parthenocarpic capacity of pro is mainly associated with changes in the expression of genes involved in GA and auxin pathways (Carrera et al., 2012). A new SlDELLA mutant containing a single nucleotide substitution, procera2 (pro2), has been recently identified and shows a potential for high fruit yield in both optimal and unfavorable growing conditions due to its facultative parthenocarpic capacity (Shinozaki et al., 2018c). Parthenocarpy is indeed an attractive trait for fruit production (Shinozaki et al., 2018c). As mentioned previously, other phytohormones are involved in fruit set and growth. A number of ABA-deficient mutants have provided valuable insights into the role of ABA in fruit growth (Azzi et al., 2015). Phenotypic characterization of the ABA biosynthesis not/flcdouble mutant showed that its small fruits had considerably reduced ABA levels and smaller cell sizes, especially within the pericarp (Nitsch et al., 2012). It was suggested that ABA stimulates fruit growth by restricting the level of ethylene in normal fruits (Azzi et al., 2015), which may indeed induce fruit set as tomato plants treated with the ethylene action inhibitor 1-methylcyclopropene (1-MCP) produce parthenocarpic fruits (Shinozaki et al., 2015). In the same way, tomato plants carrying either of two allelic mutations in ETHYLENE RECEPTOR1 (Sletr1-1 or Sletr1-2) were insensitive to ethylene, resulting in parthenocarpy (Shinozaki et al., 2015; Shinozaki et al., 2018a). Ethylene is involved in the senescence of unpollinated ovaries and prevents fruit set by downregulating GA accumulation, acting downstream of auxin and upstream of GA in the control of fruit set (Shinozaki et al., 2018a). Exogenous CK application induces parthenocarpic fruits (Matsuo et al., 2012;Ding et al., 2013), suggesting a role for CKs during tomato fruit initiation. Cytokinins induce parthenocarpy in tomato partially through modulation of GA and auxin metabolisms (Ding et al., 2013). Moreover, transcriptomic and metabolomicstudies showed that although CKs mainly controlcell division during tomato fruit development, they also play a critical role in fruit-set and early growth of tomato fruits (Mariotti et al., 2011;Matsuo et al., 2012). A key role for PAs during fruit set was also suggested, with tomato genes encoding enzymes involved in PA biosynthesis, such as arginine/ornithine decarboxylase (ADC/ ODC) and spermine synthase (SPMS), suggested to be particularly important during the process of fruit setting (Liu et al., 2018). Fruit Ripening Fruit ripening has been widely studied in tomato, with ethylene known to play a key role in this process (Osorio et al., 2013; Seymour et al., 2013;Liu et al., 2015;Borghesi et al., 2016; Shinozaki et al., 2018b;Li et al., 2019a)(Figures 1C, D). Two systems of ethylene biosynthesis have been proposed in climacteric fruits (McMurchie et al., 1972): System 1 is responsible for producing basal ethylene levels during fruit growth and is ethylene autoinhibitory, while system 2 operates during climacteric ripening and is autocatalytic (Liu et al., 2015). At the onset of ripening, an increase in ethylene is observed in mature greentomatoes, resultinginaneventual100-to300-foldincreasein the ethylene concentration during fruit ripening (Karlova et al., 2014;Li et al., 2019a). Ethylene initiates a cascade ofchanges, which culminate in the transformation of the hard, unpalatable green tomato into an attractive, brightly colored succulent and nutritious fruit (Giovannoni, 2004;Li et al., 2019a). Ethylene signaling can be regulated at several levels, including ethylene biosynthesis and its perception (Karlova et al., 2014; Mata et al., 2018;Li et al., 2019a). Ethylene biosynthesis involves multiple aminocyclopropane-1-carboxylic acid (ACC) synthase and ACC oxidase enzymes and genes (Osorio et al., 2013; Karlova et al., 2014;Kou et al., 2016;Li et al., 2019a). Fourteen putative ACS genes and six ACO genes have been identified in the tomato genome (Liu et al., 2015). Among them, it has been proposed that SlACS2,SlACS4,SlACO1,SlACO2, and SlACO4 play important roles in ethylene production during tomato fruit maturation (Cara and Giovannoni, 2008;Liu et al., 2015). Some transcription factors are known to act upstream of the ethylene biosynthesisgenestoregulatefruitripening,includingRIN,SlHB-1, and the NAC transcription factors SNAC4 and SNAC9 (Liu et al., 2015;Kou et al., 2016). Ethylene perception is mediated through ethylene receptors encoded by ETHYLENE RESPONSE (ETR) genes, which activate Quinet et al. Tomato Fruit Metabolism Frontiers in Plant Science | www.frontiersin.org November 2019 | Volume 10 | Article 15546 a signal transduction cascade through the release of the block on ETHYLENE INSENSITIVE2 (EIN2) exerted by CONSTITUTIVE TRIPLE RESPONSE1 (CTR1)(Karlova et al., 2014;Liu et al., 2015;Mata et al., 2018;Li et al., 2019a). Seven ETR genes and four CTR1 homologs have been identified in tomato thus far, all of which control ethylene sensitivity by balancing the turnover of the components of the ethylene signaling pathway, combining positive and negative feedback (Liu et al., 2015;Mata et al., 2018). This release then activates the EIN3/EIN3-like (EIL) primary transcription factor genes, resulting in the expression of secondary transcription factor genes encoding the ethylene response factors (ERFs) (Karlova et al., 2014;Liu et al., 2015; Mata et al., 2018). The final result of this signaling pathway is the transcriptional regulation of the target genes by the EILs or ERFs (Karlova et al., 2014). Some of the ERF genes have been characterized in tomato, including SlERF1,SlERF.B3,and SlERF6 (Li et al., 2007;Liu et al., 2013;Karlova et al., 2014), but many of their functions and ethylene-responsive target genes remain unknown (Li et al., 2019a). Six EIL genes have been identified in tomato, although SlEIL5 and SlEIL6 may not be involved in tomato ripening (Liu et al., 2015). Several genes that regulate tomato ripening through the transduction of ethylene signals have been identified (Karlova et al., 2014), including the ethylene receptor genes NR,ETR6, and GREEN-RIPE (Gr)(Yen et al., 1995;Barry and Giovannoni, 2006;Kevany et al., 2007). Two other proteins, RESPONSE TO ANTAGONIST1 (RAN1) and TETRATRICOPEPTIDE REPEAT1 (TRP1), also play important roles at the receptor levels (Liu et al., 2015). Ripening is also influenced by the balance of other hormones, including ABA, auxin, and the brassinosteroids (Seymour et al., 2013;Karlova et al., 2014;Liu et al., 2015;Shinozaki et al., 2018b; Li et al., 2019a;Shin et al., 2019). ABA is known to promote ripening, whereas auxin seems to have an antagonistic effect (Liu et al., 2015). ABA is a key intermediate regulator of tomato fruit ripening, and its levels change according to fruit development stages (Zhang et al., 2009;Borghesi et al., 2016). In tomato, the suppression of the gene that catalyzes the first step in ABA biosynthesis [9-cis-epoxy carotenoid dioxygenase (NCED1)] results in the downregulation of some ripening-related cell wall genes, such as those encoding polygalacturonase and pectin methylesterase, promoting an increase in firmness and a longer shelf life (Sun et al., 2012). ABA interacts with ethylene signaling; the expression of genes involved in ethylene biosynthesis are induced by exogenous ABA (Liu et al., 2015). Low levels of auxins are also required at the onset of ripening, and auxin signaling declines at this stage (Gillaspy et al., 1993; Karlova et al., 2014;Shin et al., 2019); however, it seems that the ratio between indole acetic acid (IAA) and its conjugated forms is more important than the level of free IAA for the regulation of tomato ripening (Karlova et al., 2014). Indeed, the decrease of free IAA at the onset of ripening is associated with an increase in its conjugated form, IAA-Asp (Buta and Spaulding, 1994; Karlova et al., 2014). SlSAUR69 is involved in the decrease of auxin levels and/or signaling in the pericarp tissue at the onset of fruit ripening via the repression of polar auxin transport (Shin et al., 2019). ARF genes are also involved in fruit ripening; the downregulation of SlARF4 or SlARF2 resulted in fruits with dramatic ripening defects (Jones et al., 2002;Karlova et al., 2014;Hao et al., 2015). Auxin–ethylene interactions are crucial for the fruit ripening process, although the molecular basis of the regulatory network is still relatively unclear (Li et al., 2017;Shin et al., 2019). An antagonistic effect between auxin and ethylene has been observed during the ripening of tomatoes (Li et al., 2017), with ethylene inhibiting auxin transport, metabolism, and signaling processes, while auxin represses the expression of genes involved in ethylene biosynthesis and signaling (Chaabouni et al., 2009;Liu et al., 2015;Li et al., 2016a;Li et al., 2017). Moreover, both auxin and ethylene differentially regulate CK metabolism and signaling processes during tomato ripening (Li et al., 2017). Brassinosteroids might also be involved in tomato ripening, as exogenous applications of this hormone can promote ripening and ethylene production in tomatoes (Karlova et al., 2014). PAs are also actively involved in climacteric fruit ripening (Liu et al., 2018); for example, putrescine levels progressively increase during fruit maturation and peak in ripe tomatoes, while spermine and spermidine levels decrease gradually until the fruits are fully ripe (Tsaniklidis et al., 2016;Liu et al., 2018). Moreover, although the expression levels of SPMS,ADC, and ODC were minimal during the fruit ripening process, the SPDS genes may play an important role during tomato fruit ripening (Liu et al., 2018). Phytohormones also play a key role in the regulation of tomato fruit metabolism and quality (Van Meulebroek et al., 2015;Cruz et al., 2018;Li et al., 2019b). The hormones discussed above all contribute to the metabolism of tomato fruits, although ABA and ethylene play the most important roles (Li et al., 2019b). ABA had a greater effect on the regulation of the primary metabolism, while ethylene plays an important role in the transition of primary to secondary metabolism in tomatoes (Li et al., 2019b). Regarding secondary metabolism, ethylene and auxins were described as the most important regulators of carotenoid biosynthesis during tomato fruit ripening (Van Meulebroek et al., 2015;Cruz et al., 2018). PRIMARY METABOLISM IN TOMATO FRUIT Development of the tomato fleshy fruit occurs in three distinct phases : i) cell division phase occurs in the early days following fertilization until 10 DAA ii) cell expansion (from 10 DAA to 40 DAA) and iii) fruit ripening and maturation (Figure 1A). During this evolution, tomato fruits follows a transition from partially photosynthetic to complete heterotrophic metabolism. Typical morphophysiological steps are considered and include immature, mature green, breaker, pink and red ripe fruits. Although the fruit ripening is an important step determining the fruit quality and nutritional values, recent works provided evidences that the early fruit development also assumes key roles for acquisition of quality traits, including the accumulation of sugars and organic acids Quinet et al. Tomato Fruit Metabolism Frontiers in Plant Science | www.frontiersin.org November 2019 | Volume 10 | Article 15547 (Carrari and Fernie, 2006;Beauvoit et al., 2014;Biais et al., 2014; Bauchet et al., 2017). Postgenomic approaches including analyses of fruit transcriptomes, proteomes, and metabolomes as well as multilevel studies integrating enzyme profiling generated a largeset of useful data improving our knowledge on the regulation of metabolites turnover during tomato fruit development (Mounet et al., 2009;Centeno et al., 2011;Van de Poel et al., 2012;Van Meulebroeketal.,2015).HierarchicalclusteringperformedbyBiais et al. (2014) revealed tight associations between enzyme activities and developmental phase and concluded that metabolites are more sensitive to growth conditions than enzyme activities. A global overview of the main recorded changes in metabolites recorded duringfruittransitionfromgreentoredmaturefruitsisprovidedin Figure 2. Carbohydrate Metabolism Immature Green Fruit Photosynthesis Sugars are closely related to fruit yield and quality. In tomato fruits, sugars provide sweetness and are important for the generation of turgor pressure to promote cell expansion (Kanayama, 2017). Sugars also act as signal molecules controlling fruit development and metabolism. Green fruits remain able to perform photosynthesis which can produce up to 20% of the fruit photosynthetates, the remaining part being imported by source leaves (Pesaresi et al., 2014). The light harvesting electron transfer and CO 2 fixation proteins are conserved in their active state in green fruit tissues (Matas et al., 2011). Fruit chloroplasts contain sufficient amounts of plastocyanin, ferredoxins, Rieske proteins, cytochrome fand cytochrome b 559 and ribulose-1,5-biphosphate carboxylase activity is detected in the fruits (Hetherington et al., 1998). The triose phosphate and glucose phosphate transporters are active in the tomato chloroplasts. Unexpectedly, genes associated with photosynthesis are highly expressed in the locule which is in fact the main site of respiration (Lemaire-Chamley et al., 2005). Nevertheless, the importance of green fruit photosynthesis is still a matter of debate. According to Carrara et al. (2001),tomato fruits do not show signs of CO 2 fixation, even if photochemical FIGURE 2 | Global overview of metabolic changes occurring during the transition from green expanding fruit to ripening processes (from 30 DAA to 60 DAA) in tomato fruit. Names of metabolites in red, green and black indicate increase, decrease or no changes, respectively. Metabolites are analyzed mainly in pericarps. The Figure summarizes data collected by Carrari and Fernie (2006);Gilbert (2009);Mounet et al. (2009);Centeno et al. (2011);Beauvoit et al. (2014);Biais et al. (2014), Van Meulebroek et al. (2015),Van de Poel et al. (2012), and Zhao et al. (2018). Quinet et al. Tomato Fruit Metabolism Frontiers in Plant Science | www.frontiersin.org November 2019 | Volume 10 | Article 15548 activity is detectable and an effective electron transport observed. Xu et al. (1997) reported that a small fruit (fresh weight lower than 10 g) is able to perform a gross photosynthesis equivalent to a 3cm 2 leaf blade but that this activity rapidly decreases thereafter: in heavier fruits, gross photosynthesis decreases to negligible values. These authors even assume that the aim of the photosynthetic process in maturing fruit is mainly to delete CO 2 produced by respiration rather than contributing to photosynthate production. Kahlau and Bock (2008) showed that RNA, translation and protein accumulation downregulation was observed for all plastid-encoded photosynthesis genes already in the green fruit. Hetherington et al. (1998) however demonstrated that all truss tissues, including fruits, are quite active photosynthetically. These authors interestingly demonstrated that the relative contribution of the fruit versus the leaf photosynthesis for fruit photosynthate accumulation tend to narrow under low light intensities. Afruitspecific antisense inhibition of the chloroplastic fructose 1,6-biphosphatase (FBPase) led to an obvious decrease in final weight of ripe fruits (Obiadalla-Ali et al., 2004) while, conversely, tomato lines with a fruit specific reduction in the expression of glutamate-1-semialdehyde aminotransferase (GSA) and thus a lower level of chlorophyll and photosynthetic rate, remained unaffected in terms offruit weight (Lytovchenko et al., 2011). Ntagkas et al. (2019) recently demonstrated that phosynthetically active fruits able to respond to light may trigger ascorbate synthesis while nonphotosynthetic red maturing fruits are unable to produce this antioxidant in response to light. Auxin plays an important role for determining final fruit stage through the control of cell division and cell expansion. Auxinresponsive factors (ARF) can either activate or repress transcription of auxin-responsive genes. Combined metabolomics and transcriptomic studies of plants deficient in the expression of the tomato Aux/IAA transcription factor IAA9 suggest a role for photosynthesis in the initiation of fruit development (Wang et al., 2009). Downregulation of SlARF4 enhanced fruit firmness and increased chlorophyll content in green fruits in relation to an increased number of chloroplasts (Guillon et al., 2008). SlARF4 also has a direct impact on fruit sugar metabolism: the SlARF4 underexpression tomato lines accumulated more starch at early stages of fruit development associated with an improved photochemical efficiency (Sagar et al., 2013). Moreover, SlARF4 is highly expressed in the pericarp tissues of immature fruits and undergoes decline at the onset of ripening. Down-regulated tomatoes also present a higher starch content than the wild type in developing fruits which is directly related to up-regulation of several genes and enzyme activities involved in starch biosynthesis (Sagar et al., 2013). Plastid numbers and chlorophyll content in fruits are positively correlated with photosynthesis and photosynthate accumulation and both are influenced by numerous environmental and genetic factors. In tomato fruits, the GOLDEN2-LIKE (GLK) transcription factor induces the expression of numerous genes related to chloroplast differentiation and photosynthesis (Powell et al., 2012). The genome of S. lycopersicum possesses two copies of this gene: SlGLK1 is predominantly expressed in the leaves while SlGLK2 is expressed in the fruits, especially in the area of pedicel junction (Nguyen et al., 2014). A latitudinal gradient of SlGLK2 expression induces a typical uneven coloration in ripe fruit SlGLK2 is preferentially expressed in the shoulder of the fruit (Sagar et al., 2013). Sl-GLK2 belongs to the GARP subfamily of the myb transcription factor and is encoded by the UNIFORM (U) gene (Powell et al., 2012). The umutation has been widely selected in modern tomato varieties which consequently exhibit a uniform ripening attractive to consumers and suitable for industrial processing. This mutant contains less sugar and chloroplasts present a lower number of thylakoid grana. According to Nadakuduti et al. (2014),someclassIKNOTTED1-LIKE HOMEOBOX gene (TKN2 and TKN4)alsoinfluence chloroplast development in tomato fruits and act upstream of SlGLK2. A dominant gain-of-functionmutation of TKN2 induces ectopic fruit chloroplast development that resembles SlGLK2 overexpression. More recently, Lupi et al. (2019) demonstrated that SlGLK2 expression is partly regulated by a phytochrome-mediated light perception. Auxin appears as a negative regulator of SlGLK2 expression and SlGLK2 enhances cytokinin responsiveness. This study also demonstrated that SlGLK2 enhances tocopherol and total soluble solid through amylase stimulation, so that selection of the umutation in commercial varieties probably inadvertently compromise ripe fruit quality. Sugar Unloading in Fruits Sugar unloading in tomato fruit is a controlled process and its pattern is not constant during the fruit development. In green developing fruits, sugar is mainly unloaded via the symplasm. Numerous plasmodesmata and cell connections are present at this stage (Ruan and Patrick, 1995) but then are progressively lost. During this early phase of development, only a small amount of sucrose is unloaded by the apoplastic invertase and transported into the fruit cells by hexose transporters (NguyenQuoc and Foyer, 2001;Beckles et al., 2012). Although it has been demonstrated that sucrose unloads in tomato pericarp until 35 DAA, a precocious role for apoplastic invertase has however been postulated on the basis of kinetics properties explaining a moderate QTL for Brix index (Fridman et al., 2004). Sugar Metabolism At the Cell Division Stage In growing fruits, sucrose represents less than 1% DW while fructose and glucose are the main accumulated soluble sugars (25 and 22% DW; Gilbert, 2009). Glucose and fructose content strongly increased during early fruit developmental phase. Most studies until recent year have focused on the ripe stage but omics analysis need to be conducted throughout fruit development since several interactions may occur between the different stages (Kanayama, 2017). In green fruits, hexose phosphates are mainly used for starch synthesis until 13 DPA. Starch accumulation in pericarp and columella tissues at this early stage is a key factor determining the final soluble solid content of mature fruits (Carrari and Fernie, 2006). The sink strength of a developing fruit depends on both sink activity and sink size, the latter being a function of both the number and the size of the fruit cells. According to Kataoka et al. (2009), gibberellic acid just after anthesis can promote an Quinet et al. Tomato Fruit Metabolism Frontiers in Plant Science | www.frontiersin.org November 2019 | Volume 10 | Article 15549 cultivar-dependent (Atkinson et al., 2011;Sánchez‐Rodríguezetal., 2012). In contrast to salinity and drought, heat mainly decreased the concentration of pigments and ascorbic acid in tomatoes (Li et al., 2012;Hernández et al., 2015) and increased CO 2 levels decreased carotenoid, polyphenol and flavonoid concentrations but increased ascorbic acid concentration in tomatoes (Mamatha et al., 2014). All these compounds play an important role in the final nutritional and commercial quality of tomato and depend on genetic, environmental, agronomic and post-harvest factors (Flores et al., 2016). Several studies based on the influence of these factors on fruit composition have been carried out with the aim of increasing tomato quality (Flores et al., 2016). In addition to the environmental conditions to which plants are subjected during their growth, post-harvest conditions may also affect fruit quality and metabolism. The impact of low temperature storage on tomato quality has been extensively investigated (Sevillano et al., 2009;Luengwilai et al., 2012; Cruz-Mendívil et al., 2015;Wang et al., 2015;Raffo et al., 2018; Zhang et al., 2019). Among others, early harvesting and cold storage negatively affect tomato flavor and decrease the levels of aroma compounds (Wang et al., 2015;Raffo et al., 2018). Indeed, metabolomics data showed that 7 amino acids, 27 organic acids, 16 of sugars and 22 other compounds had a significantly different content in cold-stored tomatoes and transcriptomics data showed 1735 differentially expressed genes due to cold storage (Zhang et al., 2019). Some pre-treatments have been proposed to improve tomato fruit resistance to cold stress such as ozone exposition, high CO 2 treatment, UV-C hormesis, oxalic acid application and heat treatment (Moretti et al., 2010; Luengwilai et al., 2012;Mattos et al., 2014;Charles et al., 2015; Cruz-Mendívil et al., 2015;Li et al., 2016b;Sangwanangkul et al., 2017;Raffo et al., 2018). These treatments provide protection from chilling in part by altering levels of fruit metabolites (Luengwilai et al., 2012;Wang et al., 2015;Sangwanangkul et al., 2017). CONCLUSIONS In this review, we focused on the tomato fruit development and metabolism.Tomatohaslongbeenthemodelforthestudyoffleshy fruits and the emergence of “omics”approaches (phenomics, genomics, transcriptomics, proteomics, and metabolomics) has largely contributed to improve our understanding of the genetic, hormonal and metabolic networks that govern tomato fruit development and metabolism. Tomatoes are climacteric fruits with high level of health-promoting compounds. As important as yield improvement and stress resistance, enhancement of tomato fruit quality has gained extensive attention. Improvement of tomato flavor and quality is a challenge for the coming years. The sequencing of tomato genome and genome-wide association studies provide genetic insights into the genetic control of tomato flavor and gives a roadmap for flavor improvement. Moreover, several techniques can now be exploited for breeding superior tomato varieties in the context of current changing climatic conditions. AUTHOR CONTRIBUTIONS MQ and SL designed the outline of the manuscript. MQ, SL, FY-L, TA, and J-PM contributed to writing and revisions of the manuscript. SB and RB-G contributed to figure design and revisions of the manuscript. All authors read and approved the final manuscript. FUNDING This work was supported by funding from the Belgium “Fonds National de la Recherche Scientifique (FRS-FNRS)”(grant no. CDR J.0136.19). ACKNOWLEDGMENTS The authors are grateful to Jennifer Mach for language improvement. RB-G is grateful to the FSR (Fonds special de recherché) for the award of a research fellowship. This work was published with the support of the University Foundation of Belgium. REFERENCES Adamski, N. M., Anastasiou, E., Eriksson, S., O’Neill, C. M., and Lenhard, M. (2009). Local maternal control of seed size by KLUH/CYP78A5-dependent growth signaling. PNAS 106, 20115–20120. doi: 10.1073/pnas.0907024106 Adato, A., Mandel, T., Mintz-Oron, S., Venger, I., Levy, D., Yativ, M., et al. (2009). Fruit-surface flavonoid accumulation in tomato is controlled by a SlMYB12regulated transcriptional network. PloS Genet. 5, e1000777. doi: 10.1371/ journal.pgen.1000777 Agarwal, S., and Rao, A. V. (2000). Tomato lycopene and its role in human health and chronic diseases. 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