As defined at the European level by the European Council Regulations on organic production, organic grapes come from vineyards grown under organic farming methods. Indeed, the International Federation of Organic Agriculture Movement (IFOAM) defines organic viticulture and winemaking as a “holistic production management system which promotes and enhances agro-ecosystem health, including biodiversity, biological cycles, and soil biological activity. It emphasizes the use of management practices in preference to the use of off-farm inputs, considering that regional conditions require locally adapted systems” ^[1][2][1,2]. As of August 2012, organic wines can be labeled “organic” with the EU organic logo. This means the wine can now be appropriateerly recognized as an organic product [3]. However, and because the laws regulating organic wine production vary worldwide, the definition of “organic wine” does not have the same meaning in all places. Usually, the most essentialimportant purpose is to avoid synthetic chemical fertilizers, and pesticides, and genetically modified organisms. In many countries such as the USA, Canada, and Australia, this category of wines has been regulated sincefrom 2000, while in Europe, organic wines have been helregulated by law since 2012 (EC Regulation No. 203/2012 [4]). Nowadays, many countries, despite having some different regulations, many countries aallow organic wine agronomists and winemakers to use the term “organic wine” along with the organic logo on their label after certification. In Europe, the organic wines are certified by private structures authorized by a public authority. This regulation allows consumers to distinguish organic wines from conventional wines ^[5][6][5,6].

As European vineyards constituted over 80% of the world’s total organic grape growing area in 2014 [6], the European Union (EU) regulations on “organic wine” were an esseimportantial measure for the global organic wine market. Thus, since the organic certification and standards are defined in the EU regulation, it is possible to define exclusive standards with additional detailed production rules. M Private standards are appreciated by many winemakers and many consumers appreciate private standards as s indications of quality wine that authentically express terroir, and that aim to strengthen the subsequent aspects of viticulture and enology: (i) biodiversity in grape production; (ii) attention to soil fertility and soil life; (iii) alternative approaches to pests and diseases; (iv) sustainability of grape production and wine processing and storage; (v) quality and source of wine ingredients, including further limitations on enrichment and requirements for ingredients to be fully organic; (vi) quality of yeasts, including wild yeasts and spontaneous fermentation; (vii) further limitations on additives and further reduction or total ban of sulfites; (viii) further limitations on processing techniques; and (ix) requirements or limitations on tools and equipment [3]. Undeniably, the yeasts present on grape berries from organic vineyards have an inimitable composition and may deliver distinct regional characteristics to this kind of wine ^[7][8].

Moreover, according to European regulations, organic wine must be made of organic ingredients. Thus, additional rules for oenological practices, processes, treatments, and substances such as additives and processing aids must be considered. Many mpracticethods and meaningsubstances used in conventional production are unsuitable for organic wine production, and there are specific restrictions and limitations, requireing that organic products and substances be used if they are available.

However, despite all these wine private wine standards, wine safety, for winemakers and consumers, relies upon a complex equilibrium from good winemaking practices, quality of grapes, fermentation, and post-fermentation events. An occurrence in wine safety results in the recoveryuperation of a widebroad variety of harmful compounds for human health, such as amines, carbamate, methanol, mycotoxins, and other dangerous compounds ^[8][9].

The perceived increase in sensory complexity and superiority of successful uninoculated wine fermentations, as well as a thrust from consumers looking for a more “natural” or “organic” wine, produced with fewer additives and perceived health attributes, has led to more investigations into the uses of non-Saccharomyces yeasts in wine ^{[9][10][11][12][13]}[10,11,12,13,14].

2. Wine Contamination by Ochratoxin A (OTA) and Other Mycotoxins

Human health issues and scientific attention are focused mainly on carcinogenic/toxic mycotoxins ^[14][15][15,16]. More than 300 mycotoxins have been identified, and they are produced by filamentous fungi, mainly Aspergillus spp, Fusarium spp., and Penicillium spp. ^[16][17]. OTA is produced from fungi, namely Aspergillus spp. and Penicillium spp., and derives from 3,4-dihydrocumarin linked to an amide bond with an amino group of L-β-phenylalanine ^[17][18].[18,19], and Iit can appear in grapes (pre-harvest) and/or during pre-fermentation ^[19][20][20,21]. Its presence in wines is mainly found in red wine, followed by rosé and white wines ^[21][22][22,23]. TOchratoxin A is classified by the International Agency for Research classifies Ochratoxin A on on Cancer (IARC) ^[23][24] in group 2B (possible human carcinogen), so it is an excellengreat threat tofor humans. It accumulates in several tissues in the body, with the kidneys being its primarymain target, causing Balkan endemic nephropathy (BEN), chronic interstitial nephritis, and karyomegalic interstitial nephritis ^[8][9]. The presence of OTA in blood from healthy humans confirms continuous and widespread exposure;, thus, the Scientific Panel on Contaminants in the Food Chain from the European Food Safety Authority ^[24][25] set OTA tolerable weekly intake (TWI) to 120 ng/kg body weight ^[8][9]. OTA levels in wines depend on various factors such as weather and vineyard location, tharveste period of harvest, pesticide treatments, wine fermentation, and duration of grape maceration ^[8][9]. The European Union allows a maximum limit for OTA in the wine of 2 ng/g ^[22][23]. The wines/musts decontamination of OTA has been revised by Quintela et al. ^[25][26] and, for conventionandl wines, physical, chemical, or biological methods can be applied to conventional wines. For organic wines, owing to the restrictions imposed by IFAOM, most of the chemical treatments cannot be used once the chemical products recommended for conventional wines (chitin and chitosan, urease, polyvinylpolypyrrolidone (PVPP) ^[22][23]) are forbidden for this kind of wine. A possible way for wine decontamination could be the bioremediation ^[20][25][21,26] through toxin degradation and adsorption. Several enzymes may be involved in the microbiological degradation of OTA., Still,but not much information is available, and only a few have been characterized, including the pancreatic enzyme carboxypeptidase A (CPA) (EC 3.4.17.1) from bovine, the first protease reported to be able to hydrolyze OTA ^[26][27]. Toxin degradation can be performed by the bacteria Pediococcus parvulus ^[27][28], the bacteria Acinetobacter calcoaceticus ^[28][29], and the soil bacteria Cupriavidus basilensis ^[18][19]. These microorganisms hydrolyze the OTA amide bond and produce ochratoxin α (OT α), a non-toxic compound (Figure 1). This pathway is promising; however, the production of OTα could also be a threat, because the implication of the accumulation of this compound in the body is yet unclear. A second way for wine decontamination is OTA adsorption on the yeast cell wall during fermentation. For oenological strains, the parietal adsorption activity is a new selection feature that is attractive because it can enhance wine safety and quality ^[30][31]. Several authors proposed the yeasts as adsorbing tools under both in vitro and in vivo ^[20][31][32]conditions [21,32,33]. Several studies have also reported the interaction of yeast cells with a diversity of wine compounds, from coloring pigments such as anthocyanins ^[33][34] to sulfur compounds ^[34][35] or detrimental components such as octanoic and decanoic acids ^[35][36], pesticides ^[36][37], geosmin ^[37][38], and 4-ethylphenol ^[38][39]. The yeast parietal adsorption activity is different from yeast to yeast, depending on the structural characteristics and chemical composition of the outermost layer of the cell wall. This layer comprises made up of mannoproteins, which representing 25–50% of the entire cell wall ^[39][40]. Parietal mannoproteins relate to an inner matrix of amorphous β-1,3 glucan and are partly released in wine.

3. Organic Wines Contamination with Biogenic Amines

Biogenic amines (BAs) are low-molecular-weight organic molecules originating in fermented foods from the microbial catabolism of the corresponding amino acids. Wine BA includes putrescine (from arginine and ornithine), cadaverine (from lysine), tyramine (from tyrosine), histamine (from histidine), and tryptamine (from tryptophane) ^[8][9]; Figure 2. The production of BAs is a strategy to obtain metabolic advantages to face certain stress conditions ^[40][58]. BAs are present as salts, but, at the mouth pH, they are partly in free form, becoming reactive with other compounds responsible for the aroma of the wine;, thus, they can be accountaresponsible for sensory changes like loss of varietal character and the appearance of musty smell and flavor ^[41][42][59,60]. The intake of high amounts of dietary BA can lead to several disorders, from minor symptoms resembling allergic reactions to death in severe cases of histaminosis or tyraminosis ^[19][20]. Moreover, the synergistic effect of inhibitors of the amino oxidases, such as some drugs, putrescine, and alcohol, lead them to act as histamine enhancers ^[8][9]. Humans’ high sensitivity toward biogenic amines ingested with the diet depends on insufficient amino oxidase activity caused by drugs, genetic predisposition (histamine intolerance), gastrointestinal disease, inhibition by alcohol, acetaldehyde, and other amines like putrescine and cadaverine ^[43][44][61,62]. Arginine and histidine are the most abundant amino acids in grapes. Consequently, histamine production in wines is a huge concern, as its toxicity is amplified by the alcohol and high levels of putrescine ^[45][63]. Besides, high levels of putrescine and cadaverine negatively affect the aromatic quality of wines owing to their unpleasant smells ^[45][63]. Some factors of agronomic practice as well as of the winemaking process, can cause discrete levels of biogenic amines in the wine; that is, the fertilization of the soil (nitrogen level), the poor state of health of the grapes and presence of molds, non-regular lowering of the pH of the must and development of some non-Saccharomyces yeasts, and the activity of lactic acid bacteria responsible for malolactic fermentation (MLF) ^[46][64]. As MLF mespeciainlly occurs in red wines, higher BA amounts are usually found in red wine than in rosé, white, or sparkling wines ^[47][65]. O. oeni is the main lactic acid bacteria (LAB) species carrying out the MLF, and its capability to produce histamine has been reported ^[44][62].

4. Wines and Ethyl Carbamate Contamination

Wine, including organic wines, possesses distinct nutrients, in which various a variety of microorganisms, namely yeasts and bacteria, exist. The fermentation processes may unavoidably produce toxic products because of metabolism and side reactions, including biogenic amines (BAs) and ethyl carbamate (EC). Curiously, these compounds are generated owing to the incomplete metabolism of nitrogen-containing compounds during the fermentation process ^[48][72]. EC is mainly produced by lactic acid bacteria and through the chemical combination of urea with ethanol during wine aging. The IAREC has been upgraded Eby the IARC to a “probable human carcinogen,””, Group 2A ^[49][50][73,74]. The carcinogenicity of EC has been verified in several animal species, from rats, hamsters, and monkeys ^[49][51][73,75]. In rodents, EC has been found to cause a dose-dependent increase in carcinomas of the liver, lungs, heart, mammary gland, ovaries, skin, and forestomach, among which hepatocellular tumors appear to lincrease linearlyearly increase with EC concentration ^[50][52][74,76]. During fermentation, five metabolic pathways were identified for the formation of EC. The significmantjor precursors of the construcformation of EC contain a carbamyl group, and these includinge urea, citrulline, and carbamoyl phosphate. Furthermore, it has been shown that cyanic acid and diethylpyrocarbonate are involved in EC formation ^[50][74]. The reaction between urea and ethanol is winthe's most common metabolic pathway of EC formation found in wine. The abundance of urea in grapes makes it the most common precursor. Moreover, during ethanol fermentation, the accumulation of urea originatinged from the catabolism of arginine contributes to the reaction between urea and ethanol. Additionally, urea mainly results from the metabolism of arginine by S. cerevisiae ^[50][53][74,77]. TEC can also be formed by the reaction between citrulline and ethanol can also form EC. Grape juice already contains a certain amount of citrulline, but much of this compound has its originates in the catabolism of arginine. Moreover, the generation of citrulline is assigned to the metabolism of arginine by lactic acid bacteria (LAB) via malolactic fermentation ^[54][78]. EC, in some alcoholic beverages, may also appear das a resue tolt of the reaction between cyanic acid and ethanol and, and/or the reaction between carbamyl phosphate and ethanol. However, these are rare phenomena in wine ^[50][74]. The reaction between diethylpyrocarbonate and ammonia nowadays occurs less frequently, mainly in organic wines. The appearance of diethylpyrocarbonate stems from artificial additives. This compound was known to reduce contamination and spoilage by microorganisms (yeasts or bacteria). However, the use of diethylpyrocarbonate was abandoned dueowing to its toxicity and the undesirable side effect of EC formation ^[55][79]. To better understand the metabolic formation of EC in S. cerevisiae, urea's transport and metabolic regulation of urea in S. cerevisiae must be studied. Intracellular urea mainly results from the degradation of arginine through catalysis by arginase (Figure 3). As a toxic and poor nitrogen source for S. cerevisiae, the generated urea is usually accumulated and exported to the nearby medium via a facilitated transport diffusion system (Figure 3, ^[50][74]). S. cerevisiae metabolizes urea in two steps. First, urea is carboxylated to form allophanate by urea carboxylase. Then, allophanate is degraded to CO₂ and NH₄⁺ by allophanate hydrolase. The activities of urea carboxylase and allophanate hydrolase activities are performed by a bifunctional enzyme, urea amidolyase, encoded by the DUR1,2 genes, and silenced by nitrogen catabolic repression (NCR) ^[56][80]. The DUR3 gene encodes urea permease. Under fermentation conditions, degradargininetion is obstructs degradationed by arginine, which is abundant in fermented sources and acts as a superior nitrogen supply compared with urea ^[50][74]. Several methods have been proposed for decreasing EC in wines: (i) the modification of raw materials (established recommendations on vineyard fertilization, cultivars, and nutrient status/additions, including avoiding excessive fertilization with urea, ammonia, and other N-fertilizers) and the optimization of fermentation processing parameters (such as temperature, light irradiation, pH, oxygen, and storage time); (ii) the addition of acid urease (commercial grade acid ureases are currently acquired mainly from L. fermentum) ^[57][81]; and (iii) the modification of the fermentation bacterium. All these approaches aim to reduce EC precursors ^[50][74]. However, the most common type of management in the wine industry is based on the usinge of a commercial urease enzyme that can , able to remove all of the urea andthat can evolve into ethyl carbamate ^[58][82]. Researchers have also focused on the immobilization of acid urease, possessing the advantages of facilitating enzyme recycling, reducing cost, and improving stability and resistance to inhibitory compounds ^[59][83]. However, dueowing to organic wine fermentation restrictions, urease cannot be used to treat this kind of wine [3]. Thus, the usinge of non-Saccharomyces species with urease activity allows the removes al of the main ethyl carbamate precursor from wine, making it virtually impossible for ethyl carbamate to appear during wine aging ^[60][84].