foods Review Metabolomics as a Tool to Study Underused Soy Parts: In Search of Bioactive Compounds Felipe Sanchez Bragagnolo 1,2, Cristiano Soleo Funari 1, Elena Ibáñez 2 and Alejandro Cifuentes 2,* 1 School of Agricultural Sciences, São Paulo State University (UNESP), Botucatu 18610-034, SP, Brazil; [email protected] (F.S.B.); [email protected] (C.S.F.) 2 Laboratory of Foodomics, Institute of Food Science Research (CIAL-CSIC), 28049 Madrid, Spain; [email protected] * Correspondence: [email protected] Abstract: The valorization of agri-food by-products is essential from both economic and sustainability perspectives. The large quantity of such materials causes problems for the environment; however, they can also generate new valuable ingredients and products which promote beneficial effects on human health. It is estimated that soybean production, the major oilseed crop worldwide, will leave about 597 million metric tons of branches, leaves, pods, and roots on the ground post-harvesting in 2020/21. An alternative for the use of soy-related by-products arises from the several bioactive compounds found in this plant. Metabolomics studies have already identified isoflavonoids, saponins, and organic and fatty acids, among other metabolites, in all soy organs. The present review aims to show the application of metabolomics for identifying high-added-value compounds in underused parts of the soy plant, listing the main bioactive metabolites identified up to now, as well as the factors affecting their production. Citation: Bragagnolo, F.S.; Funari, C.S.; Ibáñez, E.; Cifuentes, A. Keywords: Glycine max; foodomics; agricultural waste Metabolomics as a Tool to Study Underused Soy Parts: In Search of Bioactive Compounds. Foods 2021, 10, 1308. https://doi.org/10.3390/ 1. Introduction foods10061308 1.1. Metabolomics Applied to Agri-Foods and Their By-Products Plants have been used to produce food, feed, energy, biomaterials, and also as a source Academic Editors: Mohamed Farag of bioactive compounds. Metabolomics has emerged as one of the principal contributors and Ludger A. Wessjohann to enhancing the identification of these compounds, generating innovative discoveries and supporting the development of novel products [1]. Progress in efficient extraction Received: 11 May 2021 techniques, such as ultrasound, microwave, and pulsed-electric-field-assisted extractions, Accepted: 3 June 2021 Published: 7 June 2021 as well as supercritical fluid and pressurized liquid extractions, among others, generate ex- tracts with a higher yield and bioactivity [2–6]. Once these extracts are generated, they can Publisher’s Note: MDPI stays neutral be analyzed with one or more powerful chromatography and/or electrophoresis techniques with regard to jurisdictional claims in coupled to high-resolution mass spectrometry (MS) or nuclear magnetic resonance (NMR), published maps and institutional affil- producing accurate chemical information on a vast number of compounds [7–12]. For iations. the identification of metabolites, databases have been increasingly updated, crosslinking information from different libraries. Sorokina and Steinbeck [13] list almost one hundred databases useful for natural product research. In addition, Global Natural Product Social Molecular Networking (GNPS) and Small Molecule Accurate Recognition Technology (SMART 2.0) are examples of bio-cheminformatics tools for the analysis of MS and NMR Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. data, respectively [14–16]. All these modern techniques and tools support the advancement This article is an open access article of metabolomics’ frontiers. distributed under the terms and In 2019, 8.3 billion metric tons of cereals, oil crops, roots and tubers, sugar crops, and conditions of the Creative Commons vegetables were produced [17]. However, it is estimated that one-third of food production Attribution (CC BY) license (https:// is lost and wasted, and this problem is Target 12.3 of the 17 Sustainable Development Goals creativecommons.org/licenses/by/ (SDGs) set by the United Nations (UN) [18–20]. In this context, foodomics has shown the 4.0/). potential not only of foods, but also of their related by-products, as sources of compounds Foods 2021, 10, 1308. https://doi.org/10.3390/foods10061308 https://www.mdpi.com/journal/foods Foods 2021, 10, x FOR PEER REVIEW 2 of 18 Foods 2021, 10, 1308 Goals (SDGs) set by the United Nations (UN) [18–20]. In this context, foodomics2 ofhas 17 shown the potential not only of foods, but also of their related by-products, as sources of compounds with human health benefits (Figure 1) [21,22]. For example, Katsinas et al. [23] usedwith humansupercritical health carbon benefits dioxide (Figure and1)[ pressurized21,22]. For example, liquid extractions Katsinas etto al. valorize [23] used olive su- pomace,percritical which carbon is a dioxideby-product and of pressurized the olive oil liquid industry. extractions As a result, to valorizethey identified olive pomace, several phenolicwhich is acompounds by-product and of the generated olive oil bioactive industry. extr Asacts. a result, Assirati they et identified al. [24] applied several a phenolic metab- olomicscompounds approach and generated in the chemical bioactive investigation extracts. Assirati of the three et al. [major24] applied solid asugarcane metabolomics (Sac- charumapproach officinarum in the chemical) by-products, investigation leading of to the the three identifica majortion solid of sugarcane up to 111 (metabolitesSaccharum offici- in a singlenarum )matrix, by-products, with several leading of to these the identification compounds ofalready up to 111known metabolites by their inpotent a single bioactive matrix, properties,with several such of these as 1-octacosanol, compounds already octacosanal, known orientin, by their and potent apigenin-6-C-glucosylrham- bioactive properties, such noside.as 1-octacosanol, Terpenes octacosanal,of orange (Citrus orientin, sinensis and apigenin-6-C-glucosylrhamnoside.) juice by-products showed antioxidant Terpenes and of neuroprotectiveorange (Citrus sinensis potential) juice in by-products in vitro assays, showed as revealed antioxidant by andSánchez-Martínez neuroprotective et potential al. [25]. Asin infor vitro theassays, permeability as revealed of the by blood–brain Sánchez-Mart barrier,ínez et al.some [25 ].terpenes As for theof permeabilityorange extract of demonstratedthe blood–brain a high barrier, capacity some terpenesto cross this of orange obstacle, extract which demonstrated is a critical apoint high for capacity treating to Alzheimer’scross this obstacle, disease which [25,26]. is a critical point for treating Alzheimer’s disease [25,26]. Figure 1. Foodomics proposesproposes aa holisticholistic approach approach to to develop develop ingredients ingredients and and products products with with health health benefits benefits from from foods foods and andtheir their by-products. by-products. 1.2. Glycine max: More Than Beans 1.2. Glycine max: More Than Beans Soy, also known as soybean (Glycine max (L.) Merr.), is originally from China and EasternSoy, Asia also [ 27known]. It is as the soybean major oilseed (Glycine crop max worldwide, (L.) Merr.), with is originally a world production from China of and 362, Eastern254, and Asia 61 million [27]. It is metric the major tons ofoilseed soy grains, crop worldwide, meal, and oil,with respectively, a world production in 2020/21. of 362, For 254,the sameand 61 period, million the metric global tons area of harvestedsoy grains, was meal, 1.28 and million oil, respectively, km2, 2.5 times in 2020/21. the area For of theSpain same [28 period,,29]. Figure the global2 shows area soybean harvested production was 1.28 from million 2000/01 km², to 2.5 2020/21, times the demonstrating area of Spain [28,29].consistent Figure growth, 2 shows with soybean few moments production of decreasefrom 2000/01 [29,30 to]. 2020/21, However, demonstrating this production con- sistentinvolves growth, just one with part few of G.moments max: the of beans. decrease Krisnawati [29,30]. However, and Adie [this31] analyzedproduction 29 involves soybean justgenotypes one part and of foundG. max an: the average beans. value Krisnawati of 1.65 and for theAdie straw:grain [31] analyzed ratio 29 in soybean soy. Therefore, geno- typesit is estimated and found that an about average 597 value million of metric1.65 for tons the ofstraw:grain soy branches, ratio leaves,in soy. pods,Therefore, and roots it is estimatedwill be left that on about the ground 597 million post-harvesting metric tons inof soy 2020/21 branches, [29,31 leaves,]. Figure pods,3 shows and roots the soilwill beof left a no-tillage on the ground soybean post-harvesting production, a in system 2020/21 which [29,31]. leaves Figure all 3 underused shows the soysoil partsof a no- on tillagethe ground. soybean Keeping production, these a materials system which on the leaves soil contributesall underused to soy mineral, parts organicon the ground. matter, Keepingand humidity these materials factors [32 on]. the In soil contrast, contribute problemss to mineral, related organic to higher matter, weed and and humidity disease factorsinfestations, [32]. In as contrast, well as greenhouse problems related gas emissions to higher caused weed byand the disease decomposition infestations, of organicas well asmatter, greenhouse require gas alternative emissions management caused by the of thedecomposition agricultural of straw organic [33– matter,38]. By