Flavonoids, as well as other polyphenolic compounds, are found commonly in plant-derived material, fruits, seeds, leaves, and even the bark of some trees, they can apport distinctive colors, and pleasant smells and alter the flavor of the foods that compose them. Common flavonoids like catechin, epicatechin-gallate, quercetin, and naringenin can be found in many easy-to-find foods such as chocolate, green tea, apples, cheery, grape, tomato, broccoli, red wine, orange, grapefruit, and lemons [25].

Epicagallotechin-gallate (EGCG) is the main flavonoid found in green tea and matcha and it is known to confer this beverage which is widely popular in many countries of Asia many properties such as antioxidant, antiproliferative, antidementia, anti-inflammatory, and cardioprotective [26–28]. Recently with the surge of COVID in the year 2020, the search for answers on how to prevent and treat the disease led to the importance of studying previous molecules that could possess antiviral activity, EGCG has proven to be a potential source to inhibit SARS-CoV-2 virus. A study by Henss et al. [29] determined that EGCG was able to inhibit the replication of certain viruses with treatments of various concentrations of EGCG, the analyzed virus were the following; SARS-CoV-2 had an infection rate diminished by 50% (IR₅₀) with concentrations of 1.73 μg, MERS-CoV had an IR₅₀ of 4.64 μg and lastly SARS-CoV had an IR₅₀ of 0.83 μg.

Quercetin is a phenolic compound found in many natural sources, some of which are fruits and vegetables, some examples include grapes, onions, and apples, but this does not mean that quercetin is only found in food sources, it can also be found in medicinal plants previously used in folklore medicine some examples of medicinal plants are Ginkgo biloba and Hypericum perforatum [30]. This compound possesses various biological activities which grant consumers, antioxidants, antimicrobial, antitumoral, antidementia, anti-inflammatory, and cardiovascular protection [27, 31, 32].

Ellagitannins are dietary compounds found in many food products, such as teas, fruits, nuts, and even medicinal herbs. Ellagitannins can be found as geraniin and corilagin, and when digested or hydrolyzed can form ellagic acid [33, 34]. Ellagitannins possess a unique property that when completely digested by the gut microbiota can form urolithins. This is a complete indication that ellagitannins the compounds were fully taken advantage of and metabolized by the body [35]. Investigations on urolithins determined their multiple benefits to human health, one of which is the prevention of brain and neuronal damage, thus possibly preventing Alzheimer’s disease [36].

Geraniin is an ellagitannin commonly found in some medicinal plants and fruits. Geraniin has been studied previously for its great antioxidant, anti-inflammatory, antihypertensive, antiproliferative, and anticarcinogenic properties [33, 37–39]. Geraniin has demonstrated the potential as a great regulator for the angiotensin-converting enzyme (ACE), which regulates Angiotensin I and II responsible for elevating blood pressure, this molecule takes great importance due to the side effects that could occur with the consumption of current ACE inhibitors, the study used various concentrations of geraniin ranging from 0.1, 0.005, 0.001, 0.0005 and 0.0001 µM these concentrations was shown to positively inhibit the activity of ACE by 55%, 75%, and 75% showing an antihypertensive activity with potential of using it with patients [40].

Ellagic acid is the result of the hydrolysis of ellagitannins such as geraniin and corilagin, but this does not mean that it cannot be found in natural food sources, pomegranates, rambutan, and various kinds of nuts possess this biological compound [41]. Ellagic acid has a lot of bioactivities as an antioxidant, antimicrobial, antifungal, anti-inflammatory, neuroprotective, and cardiovascular protection factor, among others [42–46]. This molecule has been studied as an antidiabetic compound, studies in mice by Yang et al. [47] who administered an amount of ellagic acid equivalent to 0.1% of the weight of the mice to its diet with results showing that the compounds present in the diet of the mice helped lower the blood levels of glucose and also lowering triglyceride content. Ellagic acid also functions as a gene regulator, studies by Cisneros-Zevallos et al. [48] using ellagic acid at a concentration of 50 µM every 24 h decreased lipid accumulation by lipogenesis regulation, GLUT 4 glucose transporter and adiponectin. This shows the potential of ellagic acid as a regulator in metabolic disease, one of the current pandemics in the world that has until this point not been treated as it should be.

Carotenoids are natural pigments that give vegetable sources their characteristic warm tones (orange, red, and yellow) [49]. These pigments not only give color naturally to our food preparations but can also provide the consumer with various biological activities such as antioxidant, anticancer, anti-inflammatory, antimicrobial, antifungal, antiviral, antiproliferative, and cardioprotective which are of interest to the whole population [50–54]. Some natural food sources of carotenoids include microalgae, mango, orange, papaya, pumpkins, watermelon, tomatoes, peppers, eggs, liver, crustaceans, and seafood in general [55].

A great characteristic of carotenoids is that not only plants can produce them, but some fungi, yeasts, and bacteria can produce them as a by-product of their fermentation [56]. Carotenoids have a key role in human health as a precursor for vitamin A (retinol), which has a greater biological role than what it is known for popularly by allowing us to see better, but it can also help in the differentiation, proliferation, and apoptosis of human embryonic stem cells [57].

Alkaloids are natural compounds characterized for having a nitrogen molecule in any position of the structure. They are commonly found in plants, but can also be found in animals, insects, and some microorganisms [58]. The biological activity that alkaloids possess can be very important for the treatment of diabetes, cancer, and Alzheimer’s disease [59–61]. Regarding the anticancer effect of alkaloids, vinblastine, vincristine, vindesine, and vinorelbine have anticancer effects against breast carcinogenic cells like MCF-7 and MDA-MB-231, hepatic cancer cells HepG2, HepG2/ADM and leukemia cells of K562 [62].

A continuous process is when materials or energy move uninterruptedly through a system. These processes are widely used in industries, and an example of this is in food production, in addition to offering several advantages such as efficiency, high productivity, and control. However, the continuous process presents some challenges such as higher complexity and costs [88].

SSF is adapting to continuous processes, which makes SSF more cost-effective, as continuous processes are more efficient and require fewer resources [89]. SSF has several challenges, one of them is the scale at the industrial level, and within this is the choice of the bioreactor which is the environment in which microorganisms grow and are activated [90].

The bioreactor is fundamental in the development of bioprocesses, with various types used in fermentation technologies for the production of secondary metabolites, such as bioactive compounds [91]. Most SSF bioreactors operate in batch mode, however, some effects have been to design SSF systems capable of continuous operation. One of the bioreactors that have been adapted to a continuous system is a packed bed reactor (PBR) or column-type bioreactor [74]. This type of bioreactor consists of columns where the solid substrate is supported on a perforated base, allowing air to be forced through the substrate [92].

PBR has several multiple advantages, such as simple handling, larger bed volume, and easy scale-up, in addition, they can support microbial growth for long periods of culture under low shear conditions due to the immobilization of cells within microporous matrices [90, 93].

Now, few studies report continuous bioactive compound production, however, Buenrostro-Figueroa et al. [94] reported that ellagic acid could be continuously produced from pomegranate peel ellagitannins employing a PBR with Aspergillus niger GH1 under ideal conditions. In contrast, Taavoni et al. [95] reported the continuous production of B-carotene using Rhodotorula rubra cells in an airlift bioreactor, employing fatty acids from soap waste as a carbon source.

The discontinuous process often uses a batch process, which is carried out as its name implies, in batches and is a technology suitable for SSF, so it can be carried out in trays, containers, etc. [96]. In this type of process, the microorganism that is used must be inoculated in a fermented substrate with a fixed volume, therefore, the culture medium needs to be sterilized and changed with each fermentation. Once the fermentation time is done, the result will be the biological compounds of interest that can be accumulated and recovered [97]. A batch process is easy to implement as it requires low costs, the sterilization process is not as complicated, can be easy to handle, has greater flexibility, and has a very low risk of contamination. The main disadvantages are that it has lower productivity compared to the continuous process, the process control is lower, and a higher waste generation is presented [97, 98] (Table 1).

Some studies that evaluate the recovery of bioactive compounds using SSF through a batch process can be traced back to the study of Polania Rivera et al. [85] whose research group evaluated SSF applying a batch process using aluminum trays and the resulting compounds identified the polyphenols such as gallic acid, caffeic acid, and cinnamic acid. Coronado-Contreras et al. [86] determined the content of hydrolyzable and condensed tannins (3.5 mg/g and 32.9 mg/g respectively) from prickly pear peel using SSF and using Aspergillus niger GH1 and HT3 as microorganisms, as well as demonstrating high antioxidant activity.