*3.2.3 Organic acids*

*Lactose and Lactose Derivatives*

effect [55, 56].

*3.2.2 Mushrooms*

medium presents the opportunity to create value-added products [54]. *Lactobacillus kefiranofaciens* has been identified as the most important kefiran producer. Previous study demonstrated this extracellular polysaccharide is water soluble and it has the same amounts of D-glucose and D-galactose, approximately. Kefiran has several relevant applications within the biotechnology, food and pharmaceutical industries

Kefiran is a natural EPS that offers relevant food and pharmaceutical industrial

advantages. It could be added to a formulation or it could be produced i*n situ* through fermentation processes. As a polymer, kefiran exert versatile functionality. In food industry, for example it has widely applications such as stabilizer, additive, film-forming agent and gelling agent. In recent years, it has been discovered novel nano applications of this HePs, e.g. kefiran-based bio-nanocomposites and kefiran based nanofibers. Moreover, this bio-molecule also has shown biological activity properties. Several *in vitro* and *in vivo* studies have demonstrated the ability of kefiran to increase peritoneal IgA, reduce blood pressure induced hypertension, wound healing, antioxidant activity, antitumoral activity, favor the activity of peritoneal macrophages, modulation of the intestinal immune system and protection of epithelial cells against, prevent several cancer, anti-inflammatory and prebiotic

HoPs have also potential uses in the food and pharmaceutical industries. Fructans (levan and inulin-like), α -glucans (dextran, reuteran, alternan and mutan) and β -glucans are the most important HoPs [49, 51]. HoPs such as dextran have been using in bakery products improving softness or in confectionary, ice cream, frozen and dried-food and non-alcoholic wort-based beverages as stabilser. Levan and inulin-like HoPs can be used as fat substitute and sugar replacer, respectively. Besides, these HoPs may influence human host health. For example, β-glucans have demonstrated a cholesterol-lowering effect increasing cardiovascular health. Moreover, *Lactobacillus delbrueckii* subsp. *bulgaricus* strains HoPs removed cholesterol from *in vitro* culture media. Indeed, HoPs have been recognized by their benefits on the microbial gut modulation acting as prebiotics [51].

In recent years, the use of CW for mycelial growth has been explored. CW as substrate offers a wide diversity of nutrients such as proteins, carbohydrates, lipids, vitamins and minerals. On the other side, the metabolism of mycelia of fungi produced edible mushrooms utilizes the nutrients from the medium to bioaccumulate microelements such as Se, Fe and Zn. Therefore, the use of CW for mycelial growth may be a valuable nutritional supplement, reducing the impact of discharging CW

The nutritional, culinary and nutraceutical properties of mushrooms have attracted the researchers, pharmacists and nutritionists attention. The chemical composition of mushrooms includes bioactive molecules such as polysaccharides, terpenoids, low molecular weight proteins, glycoproteins among others that play a key role in boosting immune strength, lowering risks of cancers, inhibiting of

Information on mushrooms chemical composition, nutritional value and therapeutic properties has expanded during the last few years. *Pleurotus* spp. (oyster mushrooms) are one of the most cultivated mushrooms worldwide [58]. Recently, it was demonstrated that the mycelial growth of *Pleurotus djamor* in a liquid culture medium containing CW was able to produce bioactive compounds such as ergosterol and β-glucans. The addition of selenium to the medium decreased

to the environment and biofortifies mushrooms composition.

tumoral growth, maintaining of blood sugar, etc. [57].

[52]. Therefore, increasing attention has been paid to these EPS.

**82**

Several organic acids are produced during the metabolic pathways of the fermentation processes. Some organic acids e. g. lactic acid, propionic acid, butyric acid, isobutyric acid, acetic acid, capric acid, caproic acid, caprylic acid, lactobionic acid, etc., are responsible for characteristic flavors [60, 61]. However, they play a key role as functional compounds enhancing health-promoting effects and well-being. It has been demonstrated that conjugated linoleic acid (CLA, 9,11- Octadecadienoic acid, MW, 280.4 g/mol) modulate the fatty acid composition of the liver and adipose tissue of the host [62]. Indeed, succinic acid (C4H6O4, MW, 118.09 g/mol) has shown its ability to stabilize the hypoxia and cellular stress conditions focusing on the maintenance of homeostasis in aging hypothalamus. Therefore, it is hypothesized that succinate has the potential to restore the loss in functions associated with cellular senescence and systematic aging [63]. Most of the commercial succinic acid production is done by chemical technologies like catalytic hydrogenation or electrolytic reduction of maleic anhydride. In the last years, it was found that it can be produced using CW and lactose as substrates by *Actinobacillus succinogenes* 130Z in a batch fermentation [64].

According to the international market demands, lactobionic acid, fumaric acid and glucaric acid are classified as high value-added compounds [61]. These organic acids have demonstrated potential uses in food, medicine, pharmaceutical, cosmetic and chemical industries [61, 65, 66]. Glucaric acid (C6H10O8, MW, 210.14 g/mol) is found in vegetables and fruits, mainly grapefruits, apples, oranges and cruciferous vegetables. Commercially, it is synthetized by chemical oxidation of glucose releasing toxic byproducts. Thus, microbial fermentation of glucose by *Saccharomyces cerevisiae* and *Escherichia coli* has been proposed as alternative. This organic acid and its derivatives increases detoxification of carcinogens compounds and tumor promoters [67, 68]. Fumaric acid (trans-1,2-ethylenedicarboxylic acid, MW, 116.07 g/mol) is traditionally synthetized from maleic anhydride, which in turn is produced from butane. Nowadays, the production of this organic acid may be done by fermenting glucose through the metabolic pathways of *Rhizopus* species, also fixing CO2. Fumaric acid is widely used as starting material for polymerization and esterification reactions to produce paper and unsaturated polyester resins. In medicine field, it can be used to treat psoriasis, meanwhile it is also used as food and beverage additive. Moreover, Fumaric acid supplements have the ability to reduce methane emissions of cattle [66].

Lactobionic acid (4-O-ß -galactopyranosyl-D-gluconic acid, MW, 358.3 g/mol) is a high value-added lactose derivative. This organic acid has received growing attention due to its multiple applications in cosmetics, chemical, pharmaceutical, biomedicine, and food industries [61]. Lactobionic acid production is based on chemical synthesis requiring high amounts of energy and costly metal catalysts [69]. Nowadays, lactobionic acid is able to be bio-produced either through enzymatic or microbial biosynthesis at cost-effective and environmentally friendly using cheese whey lactose. In fact, high-level production of it has been recently reported controlling pH and temperature during the fermentation of lactose with *Pseudomonas taetrolens* [70]. Lactobionic acid offers wide versatile uses in nanotechnology, tissue engineering and drug-delivery systems, antibiotics, preservative solutions for organ transplantation, anti-aging, regenerative skin-care, sugar-based surfactant. Also, this value-added compound functions as food additive, gelling agent, solubilizing agent, sweetener, water holding capacity agent and bioactive ingredient enhancing calcium absorption, antioxidant activity and exerting prebiotic effects [61].

Lactic acid (2-hydroxipropionic acid, MW 90.08 g/mol) is an organic acid with a prime position due to its versatile applications in textile, leather, chemical, pharmaceutical and food industries. Lactic acid applications associated to food and food-related represent 85% of total production, approximately. This organic acid has been recognized as GRAS by the FDA [71]. It is used as flavoring, buffering agent, inhibitor of bacterial spoilage, acidulant, dough conditioner and emulsifier [72]. Most of lactic acid is produced through microbial fermentation, mainly *Lactobacillus delbrueckii or Lactobacillus amylophilus* strains, using beet extracts, molasses, starchy and cellulosic materials and cheese whey [71].

Polylactic acid is a biocompatible polymer with unique properties. Lactic acid and lactide are the building blocks to obtain it through a polycondensation reaction. This biodegradable and renewable biopolymer is a relevant alternative to plastics derived from petrochemicals, so its demand has been increasing considerably. In fact, the global polylactic acid market was expected to grow over 1.2 million tons in 2020. Nowadays, most polylactic acid is manufactured for single-use applications in packaging, including food packaging supplies [73]. However, it has important biomedical uses, due to its GRAS status recognized by the FDA. This biomaterial has been transformed into sutures, scaffolds, cell carriers and drug delivery systems such as liposomes, polymeric nanoparticles, dendrimers and micelles [74, 75].
