Genetic modifications can be related to different species and cultivar/variety of soybean. Lu et al. [51] investigated the metabolic changes between two soybean species (Glycine max and Glycine soja) under salt stress. Using gas chromatography coupled to mass spectrometry (GC–MS) and liquid chromatography coupled to Fourier transform and mass spectrometry (LC–FT/MS), the authors found a higher content of hormones, reactive oxygen species, and other substances related to the salt stress condition. In another study, Glycine max and Glycine gracilis presented different profiles of secondary metabolites during the growth stage, as revealed by a ¹H NMR-based metabolomics approach [52]. The advancement of molecular biology provides the development of a wide range of soybean cultivars or varieties, with new types of plants resistant against insects, abiotic stress, and other factors. The United States Patent and Trademark Office (USPTO) database reveals 4869 patents for a “soybean cultivar” or “soybean variety” search [53]. Different colored soybeans, such as brown, yellow, or black, present specific metabolite profiles [54,55,56]. Isoflavones could be the substrate for the production of proanthocyanidin in the seed coat, being a possible cause for the brown color of the cultivar Mallikong mutant [55]. Yang et al. [56] identified higher levels of anthocyanin and protein in yellow cotyledon seeds of black soybean. In contrast, higher levels of isoflavone, stearic acid, and polysaccharide are related to the green cotyledon seeds of the same species. Two Korean soy cultivars, Sojeongja and Haepum, presented different levels of soyasaponins Aa and Ab, whose production is related to specific gene variations [57]. Another important factor in genetic modification is the transgenic soybean. García-Villalba et al. [58] used capillary electrophoresis time-of-flight mass spectrometry (CE-TOF-MS) to qualitatively and quantitatively measure the metabolites of transgenic and non-transgenic soybeans. In summary, similar types and amounts of metabolites were identified. The same result was achieved by Harrigan et al. [59] and Clarke et al. [60]. However, it is reported that transgenic soybeans were less affected by generational effects and can present more secondary metabolites, such as prenylated isoflavones [61,62].

Moreover, the interaction between soy and microorganisms, nematodes, aphids, and other insects causes distinct metabolic responses, and metabolomics is a unique approach for understanding such changes, providing insights to improve soy’s response against biotic factors [63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80]. Recent works used GNPS to identify metabolite variation in soy infected by the fungus Phakopsora pachyrhizi and the nematode Aphelenchoides besseyi [78,79,80]. Both pathogens resulted in a higher production of bioactive compounds such as flavonoids, isoflavonoids, and terpenoids.

Distinct metabolic responses have also been reported for each growth stage of soybean [81,82,83]. During germination, 58 metabolites were reported in the separation of soy sprouts, such as phytosterols, isoflavones, and soyasaponins [84]. The production of secondary metabolites such as daidzein, genistein, and coumestrol also changed in the vegetative and reproductive soybean stages, as described by Song et al. [85].

The presence of soybean crops in a wide range of latitudes and longitudes is a consequence of several adaptive changes in their metabolism. Brazil, which is the major producer of soybean, presents different soil and climate types; even so, there is soy production in all its regions. This fact corroborates the high performance of soybean in several abiotic conditions. In addition, treatments with fertilizers and other agricultural inputs have been tested for the cultivation of soybeans in unfavorable conditions, causing additional modifications in soy metabolism [86,87,88,89,90,91,92,93,94]. As an example of external treatments, ethylene application on soybean leaves increased the genistin, daidzin, malonylgenistin, and malonyldaidzin production [94]. Using two ionization methods, electrospray ionization (ESI) and matrix-assisted laser desorption ionization (MALDI), coupled to Fourier transform ion cyclotron resonance-mass spectrometry (FTICR-MS), Yilmaz et al. [95] analyzed the metabolite profile of soy leaves from midsummer to autumn. They found a decreased production of chlorophyll-related metabolites and a higher level of disaccharides from summer to autumn. Another metabolomic approach analyzed soy leaves from crops with different geographical localizations and identified different amounts of metabolites such as pinitol and flavonoids [96]. An excellent review performed by Feng et al. [97] summarizes the use of metabolomics in soy under abiotic stress.

Different compounds belonging to the prenol lipids category, which are recognized by their bioactivity, have already been identified in soy. Tsuno et al. [108] identified several soyasaponins, sapogenins, and isoflavones in soy root exudates. Soyasaponins have been linked to anti-obesity, anti-oxidative stress, and anti-inflammatory properties, as well as preventive effects on hepatic triacylglycerol accumulation [123,124,125,126]. Omar et al. [127] identified the potent inhibitory effects of soyasapogenol A, which is a triterpenoid, against p53-deficient aggressive malignancies. In addition, other compounds of different classes, such as fatty acyls, isoflavonoids, flavonoids, and others. Linoleic acid, naringenin, and formononetin-7-O-glucoside, which are examples of the aforementioned classes, have been related to cardiovascular health, neuroprotective effects, and anti-inflammatory properties [122,128,129]. The chemical structures of these bioactive compounds are presented in Figure 5.

Leaves and roots are the most-studied underused soy parts. 259 metabolites of 32 classes identified in soy leaves are presented [38,78,80,94,98,101,102,103,106]. Almost 90 of these compounds are flavonoids, isoflavonoids, or prenol lipids. Widely known bioactive flavonoids such as apigenin, kaempferol, rutin, and others were also identified. Apigenin has been suggested as a potential anticancer agent [130]. Glyceollin I and soyasaponin I, an isoflavonoid and a prenol lipid, presented activities against breast cancer and Parkinson’s disease, respectively [120,131]. Moreover, different soyasaponins and even trigonelline, which is an alkaloid, were found in this part of the plant. For example, the latter substance was reported to have potential for lung cancer therapy, memory function recovery, and an anti-obesity effect [132,133,134]. Figure 6 shows the chemical structures of the aforementioned metabolites.

In soy branches, 197 compounds have already been identified. The most widely reported class among these metabolites is the organooxygen compounds category (53 compounds), such as alcohols and polyols, carbohydrates and their conjugates, and carbonyl. Shikimic acid, an example of an organooxygen compound, was linked to therapeutic effects in osteoarthritis [135]. Metabolites of other classes, such as succinic and stearic acids, presented an apoptotic effect in T-cell acute lymphoblastic leukemia and antifibrotic activity, respectively [136,137]. Flavonoids and isoflavonoids, such as 7,4′-dihydroxyflavone and glycitin, presented activity against lung diseases [138,139]. The chemical structures of these compounds are shown in Figure 7.

Similarly to branches, there are few metabolomics works identifying pod metabolites [38,98,100,104,105,107]. Amino acids, peptides, and mono-, di-, and tricarboxylic acids and their derivatives are the most mentioned types of compounds in pods, with some of these substances already widely used in industry, such as citric and fumaric acids. Moreover, specialized metabolites such as camphene and α-pinene, which were also identified in soy pods, presented anti-skeletal muscle atrophy and neuroprotective effects, respectively [140,141]. Quercetin, which is a widely known flavonoid, may be a potential anti-inflammatory treatment in patients with COVID-19, as described by Saeedi-Boroujeni and Mahmoudian-Sani [142]. Hexadecanoic acid, a fatty acyl compound, presented an inhibitory effect on HT-29 human colon cancer cells [143]. Figure 8 presents the chemical structures of one compound of each class mentioned. In addition, fatty acyls, flavonoids, isoflavonoids, and other classes of compounds were identified in pods.