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Quantitative data of Cunnghamella echinulata originated from cultures in media containing 0.5 g/L ammonium sulfate and initial glucose (Glc0, g/L) concentrations 25, 30, and 70 g/L. Data concern yields achieved at the maximum lipid accumulation. Cultures were conducted in duplicate, SE < 10%. DCW = dry cell weight; L = lipids; Glc = glucose; L/DCW = lipids in dry cell weight; DCW/Glc = dry cell weight per glucose. Glc was totally consumed when used at Glc0 25 and 30 g/L, while 47 g/L of Glc was assimilated when the Glc0 was 70 g/L.
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Polyunsaturated fatty acids, especially gamma-linolenic acid (GLA), are potentially useful agents in the treatment of cancer. Cunninghamella echinulata, a fungus species that is able to synthesize GLA, when cultivated under nitrogen limited conditions in a medium having glucose as carbon and energy source, accumulated 32–35% of lipids containing 11...
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Context 1
... of biomass and lipid yields of the cultures performed at various Glc 0 at the time when maximum DCW concentration was achieved (that was 290, 365, and 610 h after inoculation for Glc 0 25, 30, and 70 g/L, respectively) is sum- marized in Fig. 2. For Glc 0 = 25 and 30 g/L almost all glu- cose was assimilated. On the contrary, with Glc 0 = 70 g/L, only 47 g/L of glucose was taken up. From the obtained results it may be assumed that for a given initial nitrogen quantity in the medium, the more glucose was found in excess, the more DCW and lipid (in absolute values-grams per ...
Context 2
... acid composition was found at Glc 0 = 70 g/L, although GLA content in this case was found to be slightly higher, up to 18% in total lipids at the late S. Concerning the oil produced in bioreactor, it had a similar fatty acid composition to those produced in flasks with GLA concentration to be 12.9% w/w in total lipids (see Supporting information, Fig. ...
Citations
... FALS were also used by Ilc et al. in 1999, where purified GLA was utilized to examine the effects on glioblastoma cells [23]. However, due to the increased cost of lipid isolation and purification from their well-established sources, alternative ways to produce lipid preparations containing GLA are now available due to developments in microbial biotechnology, such as the previously mentioned potential utilization of Zygomycetes; for instance, Alakhras et al. in 2015 andSayegh et al. in 2015 exploited Zygomycota strains to produce lipids rich in GLA and eicosapentaenoic acid (EPA), respectively, in the form of FALS and fatty acid potassium salts (FAPS) [24,25]. The lipid mixtures generated by the two groups had a high PUFA content, and when administered to cancerous cell lines (leukemia and breast cancer cells), cytotoxicity and DNA fragmentation were observed [24,25]. ...
... FALS were also used by Ilc et al. in 1999, where purified GLA was utilized to examine the effects on glioblastoma cells [23]. However, due to the increased cost of lipid isolation and purification from their well-established sources, alternative ways to produce lipid preparations containing GLA are now available due to developments in microbial biotechnology, such as the previously mentioned potential utilization of Zygomycetes; for instance, Alakhras et al. in 2015 andSayegh et al. in 2015 exploited Zygomycota strains to produce lipids rich in GLA and eicosapentaenoic acid (EPA), respectively, in the form of FALS and fatty acid potassium salts (FAPS) [24,25]. The lipid mixtures generated by the two groups had a high PUFA content, and when administered to cancerous cell lines (leukemia and breast cancer cells), cytotoxicity and DNA fragmentation were observed [24,25]. ...
... However, due to the increased cost of lipid isolation and purification from their well-established sources, alternative ways to produce lipid preparations containing GLA are now available due to developments in microbial biotechnology, such as the previously mentioned potential utilization of Zygomycetes; for instance, Alakhras et al. in 2015 andSayegh et al. in 2015 exploited Zygomycota strains to produce lipids rich in GLA and eicosapentaenoic acid (EPA), respectively, in the form of FALS and fatty acid potassium salts (FAPS) [24,25]. The lipid mixtures generated by the two groups had a high PUFA content, and when administered to cancerous cell lines (leukemia and breast cancer cells), cytotoxicity and DNA fragmentation were observed [24,25]. ...
Cunninghamella elegans NRRL-1393 is an oleaginous fungus able to synthesize and accumulate unsaturated fatty acids, amongst which the bioactive gamma-linolenic acid (GLA) has potential anti-cancer activities. C. elegans was cultured in shake-flask nitrogen-limited media with either glycerol or glucose (both at ≈60 g/L) employed as the sole substrate. The assimilation rate of both substrates was similar, as the total biomass production reached 13.0–13.5 g/L, c. 350 h after inoculation (for both instances, c. 27–29 g/L of substrate were consumed). Lipid production was slightly higher on glycerol-based media, compared to the growth on glucose (≈8.4 g/L vs. ≈7.0 g/L). Lipids from C. elegans grown on glycerol, containing c. 9.5% w/w of GLA, were transformed into fatty acid lithium salts (FALS), and their effects were assessed on both human normal and cancerous cell lines. The FALS exhibited cytotoxic effects within a 48 h interval with an IC50 of about 60 μg/mL. Additionally, a suppression of migration was shown, as a significant elevation of oxidative stress levels, and the induction of cell death. Elementary differences between normal and cancer cells were not shown, indicating a generic mode of action; however, oxidative stress level augmentation may increase susceptibility to anticancer drugs, improving chemotherapy effectiveness.
... The FA contents for C. echinulata (CCF 3882) are consistent with those reported for C. echinulata ATHUM 4411 grown in glucose with yeast extract and ammonia as N sources [45,54], whereas they differ significantly from those reported by other authors who reported around 8-10 percentage points higher for the palmitic and oleic acid contents as well as 8-9 percentage points lower for the linoleic and linolenic acid contents [55]. These differences could be explained by the different strains analyzed or, in part, by the different extraction method (supercritical CO 2 ) utilized by these authors. ...
This study aimed to evaluate the microbial oil production by three selected strains, Mortierella isabellina, Cunninghamella echinulata, and Thamnidium elegans, after fermentation of an enzymatic hydrolysate from alkali pre-treated giant reed biomass, in comparison to a semi-synthetic medium, at three increasing nitrogen supplementation levels (0.14, 0.25, and 0.47 g/L). M. isabellina showed the fastest sugar consumption, the highest final cell and oil concentrations (10.9 and 5.6 g/L, respectively), as well as the highest cellular oil content, oil yield/g sugar consumed, and oil productivity (63.4%, 0.19 g/g, and 1 g/L/day, respectively) in the giant reed hydrolysate. The oil yield tended to decrease with an increasing nitrogen content in the cultures. Oleic acid was the most copious fatty acid in the oil for all the fungi. On the contrary, T. elegans exhibited the poorest performances. In particular, M. isabellina showed, respectively, the highest and lowest values of oleic and γ-linolenic acid (52.2 and 3.1%, on average). In comparison, C. echinulata and T. elegans showed much higher γ-linolenic acid content (15.3 and 21.6%, on average). Notably, the C. echinulata cultures showed by far the highest γ-linolenic acid concentration in both substrates (345 and 595 g/L in the giant reed hydrolysate and in the synthetic medium, respectively). Finally, the estimated biodiesel properties of all the oils fell within the limits of the U.S. standards, while the oil of M. isabellina only respected the tighter limits fixed by the E.U. regulations.
... The deprivation of nitrogen pushes C. elegans to accumulate fat in the form of PUFAs which are extracted from the rest of biomass using the Folch method and later a saponification step with LiOH follows, which transforms the lipids into soluble and drastic substances. Previous studies with Fatty Acid Lithium Salts (FALS) and Fatty Acid Potassium Salts (FAPS) administered on cancer cell lines, indicated cytotoxic effects on the cancer cells, however, the exact mechanism had to be further investigated ( Fig.1) [5]. ...
The Polyunsaturated Fatty Acids (PUFAs) are lipids of high biological value that cannot be synthesized by the human organism, therefore being absorbed solely from the diet. Their consumption has been correlated to possible anticancer effects, through intracellular oxidative stress level augmentation and through interaction with the apoptotic signaling pathways, which are downregulated inside cancer cells. In the current study, Fatty Acid Lithium Salts (FALS) derived from Cunninghamella elegans PUFAs, are administered at human (normal and cancer) cell lines. The fungus was grown on a rich in industrial grade glycerol (as a carbon source) substrate, and vast quantities of omega-3 and omega-6 PUFAs were accumulated. The mechanisms underlying PUFAs actions are investigated, focusing on the generation of Reactive Oxygen Species (ROS) as well as on the induction of cell death, following the lipids administration and absorbance.
... FAPS produced from the lipids were found to be potent inhibitor of various Gram positive and Gram negative bacteria, as well as breast cancer cells, even at low doses (29). Similarly, fatty acid lithium salts (FALS) derived from C. echinulata lipids containing GLA showed high cytotoxicity and genotoxicity inducing DNA fragmentation of HL-60 cancer cells (30). ARA performs several key physiological functions as a biogenetic precursor to the bio-active prostaglandins, prostacyclins, thromboxans, and leucotrienes (31). ...
Microbes have gained a lot of attention for their potential in producing polyunsaturated fatty acids (PUFAs). PUFAs are gaining scientific interest due to their important health-promoting effects on higher organisms including humans. The current sources of PUFAs (animal and plant) have associated limitations that have led to increased interest in microbial PUFAs as most reliable alternative source. The focus is on increasing the product value of existing oleaginous microbes or discovering new microbes by implementing new biotechnological strategies in order to compete with other sources. The multidisciplinary approaches, including metabolic engineering, high-throughput screening, tapping new microbial sources, genome-mining as well as co-culturing and elicitation for the production of PUFAs, have been considered and discussed in this review. The usage of agro-industrial wastes as alternative low-cost substrates in fermentation for high-value single-cell oil production has also been discussed. Multidisciplinary approaches combined with new technologies may help to uncover new microbial PUFA sources that may have nutraceutical and biotechnological importance.
... Fungal lipids sources have been studied for many applications such as in pharmaceutical, food additives, and biodiesel. Several investigations have shown that fatty acid lithium or potassium salts from Cunninghamella echinulata containing the γ-linolenic acid (GLA, ∆6, 9, 12-C18:3), are potentially useful agents in the treatment of cancer [4,5]. Some species of yeast have been proven capable of butter-like lipid production under limited culture conditions [6,7]. ...
Using marine-derived fungi as a source of lipid production holds promise as an alternative to industrial lipid production for health and nutrition in the future. In the present study, this strain showed a high production of lipid, about plus 80% of the total lipids in the host-derived medium. Gas chromatography analysis of fungal lipids revealed the presence of saturated (mainly palmitic acid C16: 0 and stearic acid C18: 0) and unsaturated fatty acid (mainly linoleic acid C18: 2, oleic acid C18: 1). These findings suggest this marine-derived fungus is a promising source for lipid production in various industrial applications. In particular, a fraction containing glycolipids of the crude extract exhibited potential cytotoxic activity on human oral epidermal carcinoma cell lines. This result is very interesting to further isolate and determine the molecular structure of bioactive glycolipids.
... PUFAs-rich animal feed could enhance animals' immunity and improve meat quality (Table 3 and Table 4). The specific medicinal effects and biological activities of PUFAs have been fully documented [64][65][66]. The general benefits of adding PUFAs in animal feed are presented as follows. ...
In recent years, as the algal polyunsaturated fatty acids are widely used in animal feed, the interests in the fundamental research and applied research of microalgae-based polyunsaturated fatty acids production are increasing. To support the industrial production of algal polyunsaturated fatty acids, studies in recent years have devoted numerous efforts in the algal strains screening, biosynthetic mechanisms exploration, induction conditions optimization, and algae-cultivation mode improvement. Specific factors impacting the biosynthesis of algal polyunsaturated fatty acids include temperature, illumination, salinity, and carbon supply. Two-stage cultivation is proven to be an effective method producing microalgae enriched with polyunsaturated fatty acids. In addition, the use of algal polyunsaturated fatty acids in animal feed has been proven to be a promising way to promote the sustainable development of human society. The addition of algal polyunsaturated fatty acids in feed could not only improve the fatty acid profile of animals, but also enhance the animals' immune responses. Herein, we would likely to summarize the progresses in the aforementioned fields and discuss some critical problems hindering the production and application of algal PUFAs. It is expected that this paper could not only introduce the new knowledge of algal polyunsaturated fatty acids to readers, but also point out the potential development trends of the production and application of algal polyunsaturated fatty acids in the coming future.
... The species of Cunninghamella were usually studied in secondary metabolites, such as polyunsaturated fatty acids [19][20][21]. They are also mainly isolated from soil and grow optimally from 23 to 28 C. Traditional morphologies for the classification of this genus include colonies, sporangiophores, vesicles, and sporangiola [22]. ...
The species within the family Cunninghamellaceae are widely distributed and produce important metabolites. Morphological studies along with a molecular phylogeny based on the internal transcribed spacer (ITS) and large subunit (LSU) of ribosomal DNA revealed two new species in this family from soils in China, that is, Absidia ovalispora sp. nov. and Cunninghamella globospora sp. nov. The former is phylogenetically closely related to Absidia koreana, but morphologically differs in sporangiospores, sporangia, sporangiophores, columellae, collars, and rhizoids. The latter is phylogenetically closely related to Cunninghamella intermedia, but morphologically differs in sporangiola and colonies. They were described and illustrated.
... The species of Cunninghamella were usually studied in secondary metabolites, such as polyunsaturated fatty acids [19][20][21]. They are also mainly isolated from soil and grow optimally from 23 to 28 C. Traditional morphologies for the classification of this genus include colonies, sporangiophores, vesicles, and sporangiola [22]. ...
The species within the family Cunninghamellaceae are widely distributed and produce important metabolites. Morphological studies along with a molecular phylogeny based on the internal transcribed spacer (ITS) and large subunit (LSU) of ribosomal DNA revealed two new species in this family from soils in China, that is, Absidia ovalispora sp. nov. and Cunninghamella globospora sp. nov. The former is phylogenetically closely related to Absidia koreana, but morphologically differs in sporangiospores, sporangia, sporangiophores, columellae, collars, and rhizoids. The latter is phylogenetically closely related to Cunninghamella intermedia, but morphologically differs in sporangiola and colonies. They were described and illustrated.
... In the current paper, similar and in some cases higher apoptosis was observed in the SKOV-3 cells treated with FAMEs instead of GEs. Likewise, FA lithium salts derived from C. echinulata lipids were proved effective against HL-60 human leukemia cells [13]. Morin et al. [67] and Siena et al. [68] reported that a variety of modified FAs are promising molecules in the treatment of cancers. ...
Sugar fatty acid esters, especially glucose fatty acid esters (GEs), have broad applications in food, cosmetic and pharmaceutical industries. In this research, the fatty acid moieties derived from polyunsaturated fatty acids containing single-cell oils (SCOs) ( i.e., those produced from Cunninghamella echinulata, Umbelopsis isabellina and Nannochloropsis gaditana, as well as from olive oil and an eicosapentaenoic acid (EPA) concentrate) were converted into GEs by enzymatic synthesis, using lipases as biocatalysts. The GE synthesis was monitored using thin-layer chromatography, FTIR and in situ NMR. It was found that GE synthesis carried out using immobilized Candida antarctica B lipase was very effective, reaching total conversion of reactants. It was shown that EPA-GEs were very effective against several pathogenic bacteria and their activity can be attributed to their high EPA content. Furthermore, C. echinulata-GEs were more effective against pathogens compared with U. isabellina-GEs, probably due to the presence of gamma linolenic acid (GLA) in the lipids of C. echinulata, which is known for its antimicrobial activity, in higher concentrations. C. echinulata-GEs also showed strong insecticidal activity against Aedes aegypti larvae, followed by EPA-GEs, olive oil-GEs and N. gaditana-GEs. All synthesized GEs induced apoptosis of the SKOV-3 ovarian cancer cell line, with the apoptotic rate increasing significantly after 48 h. A higher percentage of apoptosis was observed in the cells treated with EPA-GEs, followed by C. echinulata-GEs, U. isabellina-GEs and olive oil-GEs. We conclude that SCOs can be used in the synthesis of GEs with interesting biological properties.
... Microalgae and fungi are on the forefront of biotechnological interest due to their ability to produce SCOs rich in polyunsaturated fatty acids (PUFAs) of medical and nutritional interest [11][12][13][14][15][16][17]. The high PUFA content of the aforementioned lipids offers an additional interest in their use as acyl group donors in FAA synthesis, since several reports demonstrate that PUFAs or compounds containing PUFA moieties in their molecule exhibited interesting biological activities [18][19][20]. Among microalgae, Nannochloropsis is a prominent genus that includes species able to efficiently grow under non-aseptic conditions and accumulate lipids rich in PUFAs, such as eicosapentaenoic acid (EPA) [21,22]. ...
... As for fungi, genera belonging to Mucoromycota (including Mucor, Rhizopus, Umbelopsis, Lichtheimia, Cunninghamella, and Mortierella) are well known for their ability to synthesize PUFAs, especially gamma-linolenic acid (GLA), which is of great pharmaceutical interest due to its anticancer properties, while it has been used to improve premenstrual tension and various skin diseases [13,17]. Especially, Cunninghamella echinulata is an important GLA producer [13,19,23], while Umbelopsis isabellina is regarded as a promising SCO producer, being able to accumulate lipids in high percentages, though less rich in GLA [16,[24][25][26]. ...
Fatty acid amides (FAAs) are of great interest due to their broad industrial applications. They can be synthesized enzymatically with many advantages over chemical synthesis. In this study, the fatty acid moieties of lipids of Cunninghamella echinulata ATHUM 4411, Umbelopsis isabellina ATHUM 2935, Nannochloropsis gaditana CCAP 849/5, olive oil, and an eicosapentaenoic acid (EPA) concentrate were converted into their fatty acid methyl esters and used in the FAA (i.e., ethylene diamine amides) enzymatic synthesis, using lipases as biocatalysts. The FAA synthesis, monitored using in situ NMR, FT-IR, and thin-layer chromatography, was catalyzed efficiently by the immobilized Candida rugosa lipase. The synthesized FAAs exhibited a significant antimicrobial activity, especially those containing oleic acid in high proportions (i.e., derived from olive oil and U. isabellina oil), against several human pathogenic microorganisms, insecticidal activity against yellow fever mosquito, especially those of C. echinulata containing gamma-linolenic acid, and anticancer properties against SKOV-3 ovarian cancer cell line, especially those containing EPA in their structures (i.e., EPA concentrate and N. gaditana oil). We conclude that FAAs can be efficiently synthesized using microbial oils of different fatty acid composition and used in specific biological applications.
