Bioproduction process of natural products and biopharmaceuticals: Biotechnological aspects

Engineering Considerations to Produce Bioactive Compounds from Plant Cell Suspension Culture in Bioreactors

“…), leading to the overexploitation, threatening, or extinction of vegetal species [4][5][6]. In agreement with Süntar et al [7], half of the drugs used for clinical treatments are obtained out of natural sources, accounting for 185 chemical compounds approved by the FDA [8]. Due to the growing interest in obtaining phytochemicals from plant-derived secondary metabolites (PDSM), the use of biotechnologies based on the plant cell culture (PCC) results in a promising, sustainable, and environmentally friendly way of overcoming the problems related to either the traditional cultivation of medicinal plants (including variations in crop quality associated with drought or flood crops, diseases or pest attacks on plants, or the chemical synthesis of bioactive compounds, allowing a better control in the quality and higher yields of the desired products to be achieved.…”

“…Their main activities include antioxidant, anti-inflammatory, antiproliferative, anticancer, anti-neurodegenerative disorders, and chronic diseases, among other health properties [17]. These bioactive compounds are considered as plant-derived secondary metabolites (PDSM) since, in contrast to the primary metabolites, they do not play an active role in the direct metabolic process or growth of the plant, but their importance relies on their interactions with biotic and abiotic stresses in defense of the plant viability [7,18,19].…”

“…CSC may become unstable when subjected to prolonged culture times, causing differences in the quality and quantity of PDSM; this behavior is due to the consumption and reduced availability of nutrients in the culture media, in addition to genetic variations that can restrict the conservation of the high-yield cell line [9]. Among the strategies used for improving the production of PDSM in CSC is the modification in the culture media composition (different carbon, nitrogen, and phosphorous sources) for optimizing the nutrient availability during the culture time [6,9], and the use of biotic or abiotic elicitors that trigger the defense response from plant cells promoting the secondary metabolism through the introduction of chemical or physical stresses [7,51,95]. Biotic elicitors are complex compounds derived from biological sources, including plant-derived polysaccharides, such as pectin and cellulose, and microbial-derived polysaccharides, such as chitin and glucan [6,44], and plant immune-signaling molecules, such as jasmonic acid [96], salicylic acid [97,98], and methyl jasmonate [96].…”

“…The current production of various drugs, cosmetics, and food ingredients is obtained using plant cell cultures, especially in the form of CSC, as these offer several advantages over other technologies, such as better control during the production of PDSM, a larger feasibility for the scaling up of the process, and shorter production cycles, being environmentally responsible and sustainable processes. The application of CSC to obtain commercial products dates back to the 1960s [7,9,24,100]. Table 3 shows a selection of plant cell extracts that have been successfully manufactured at a commercial scale for pharmaceutical purposes.…”

Microbial synthesis of bacitracin: Recent progress, challenges, and prospects

“…Natural products played the critical roles in maintaining human health, and have been broadly applied in biomedicine, cosmetics, agriculture and chemical industry [ 1 ]. Natural products comprise a large range of compounds with various biological activities, and mostly originate from plants, marine animals, and microorganisms [ 2 ]. In recent years, microbial synthesis of natural products has attracted widespread attentions, owing to their short fermentation periods, mild reaction conditions, and sustainability [ 3 ].…”