RESUMO
The health benefits of polyunsaturated fatty acids (PUFAs) have encouraged the search for rich sources of these compounds. However, the supply chain of PUFAs from animals and plants presents environmental concerns, such as water pollution, deforestation, animal exploitation and interference in the trophic chain. In this way, a viable alternative has been found in microbial sources, mainly in single cell oil (SCO) production by yeast and filamentous fungi. Mortierellaceae is a filamentous fungal family world-renowned for PUFA-producing strains. For example, Mortierella alpina can be highlighted due to be industrially applied to produce arachidonic acid (20:4 n6), an important component of infant supplement formulas. Thus, the state of the art of strategies to increase PUFAs production by Mortierellaceae strains is presented in this review. Firstly, we have discussed main phylogenetic and biochemical characteristics of these strains for lipid production. Next, strategies based on physiological manipulation, using different carbon and nitrogen sources, temperature, pH and cultivation methods, which can increase PUFA production by optimizing process parameters are presented. Furthermore, it is possible to use metabolic engineering tools, controlling the supply of NADPH and co-factors, and directing the activity of desaturases and elongase to the target PUFA. Thus, this review aims to discuss the functionality and applicability of each of these strategies, in order to support future research for PUFA production by Mortierellaceae species.
Assuntos
Ácidos Graxos Insaturados , Mortierella , Animais , Filogenia , Ácidos Graxos Insaturados/metabolismo , Engenharia Metabólica , Saccharomyces cerevisiae/metabolismo , Carbono/metabolismo , Mortierella/genética , Mortierella/química , Ácidos Graxos/metabolismoRESUMO
This study presents an in vitro evaluation of the antitumor potential of a chitin-like exopolysaccharide (EPS, produced by Mortierella alpina) on Adrenocortical carcinoma cells (ACC) compared to mitotane, a commercial drug commonly used in ACC treatment, and known for its side effects. Techniques of cellular viability determination such as MTT and fluorescence were used to measure the cytotoxic effects of the EPS and mitotane in tumoral cells (H295R) and non-tumoral cells (VERO), observing high cytotoxicity of mitotane and a 10% superior pro-apoptotic effect of the EPS compared to mitotane (p < 0.05). The cytotoxic effect of the EPS was similar to the effect of 50 µM mitotane on tumoral cells (p < 0.05). A decrement of the lysosomal volume was also noted in tumoral cells treated with the EPS. To enhance the antitumor effect, a combination of mitotane at a lower dosage and the EPS (as adjuvant) was also tested, showing a slight improvement of the cytotoxicity effect on tumoral cells. Therefore, the results indicate a cytotoxic effect of the EPS produced by Mortierella alpina on adrenocortical carcinoma, and a possible application in biomedical formulations or additional treatments.
Assuntos
Carcinoma Adrenocortical/tratamento farmacológico , Proliferação de Células/efeitos dos fármacos , Quitina/farmacologia , Mortierella/química , Carcinoma Adrenocortical/patologia , Animais , Linhagem Celular Tumoral , Quitina/química , Chlorocebus aethiops , Humanos , Mitotano/farmacologia , Polissacarídeos , Células VeroRESUMO
The production of a chitin-like exopolysaccharide (EPS) was optimized through experimental design methods, evaluating the influence of urea, phosphate, and glucose. Under optimized conditions, up to 1.51 g/L was produced and its physicochemical characteristics were evaluated by chromatography, NMR, and FTIR spectroscopy, and rheological techniques. The results showed a homogeneous EPS (Mw 4.9 × 105 g mol-1) composed of chitin, linear polymer of ß-(1â4)-linked N-acetyl-d-glucosamine residues. The acetylation degree as determined by 13C CP-MAS NMR spectroscopy was over 90 %. The EPS biological activities, such as antioxidant effect and antitumor properties, were evaluated. To the best of our knowledge, this is the first study on the production of a new alternative of extracellular chitin-like polysaccharide with promising bioactive properties from the filamentous fungus M. alpina.
Assuntos
Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Neoplasias da Mama/tratamento farmacológico , Quitina/química , Fermentação , Mortierella/metabolismo , Polissacarídeos/farmacologia , Antineoplásicos/química , Antioxidantes/química , Neoplasias da Mama/patologia , Feminino , Glucose/metabolismo , Humanos , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Células Tumorais CultivadasRESUMO
The time courses for production of fungal biomass, lipid, phenolic and arachidonic acid (ARA) as well as expression of the genes involved in biosynthesis of ARA and lipid were examined in Mortierella alpina CBS 754.68. A significant increase in the arachidonic acid content in lipids that coincided with reduced levels of lipid was obtained. Reduced gene expression occurred presumably due to the steady reduction of carbon and nitrogen resources. However, these energy resources were inefficiently compensated by the breakdown of the accumulated lipids that in turn, induced up-regulated expression of the candidate genes. The results further indicated that the expression of the GLELO encoding gene is a rate-limiting step in the biosynthesis of ARA in the early growth phase.
Assuntos
Ácido Araquidônico/biossíntese , Vias Biossintéticas/genética , Perfilação da Expressão Gênica , Mortierella/genética , Mortierella/metabolismo , Carbono/metabolismo , Genes Fúngicos , Nitrogênio/metabolismo , Reação em Cadeia da Polimerase em Tempo RealRESUMO
The time courses for production of fungal biomass, lipid, phenolic and arachidonic acid (ARA) as well as expression of the genes involved in biosynthesis of ARA and lipid were examined in Mortierella alpina CBS 754.68. A significant increase in the arachidonic acid content in lipids that coincided with reduced levels of lipid was obtained. Reduced gene expression occurred presumably due to the steady reduction of carbon and nitrogen resources. However, these energy resources were inefficiently compensated by the breakdown of the accumulated lipids that in turn, induced up-regulated expression of the candidate genes. The results further indicated that the expression of the GLELO encoding gene is a rate-limiting step in the biosynthesis of ARA in the early growth phase.
Assuntos
Ácido Araquidônico/biossíntese , Vias Biossintéticas/genética , Perfilação da Expressão Gênica , Mortierella/genética , Mortierella/metabolismo , Carbono/metabolismo , Genes Fúngicos , Nitrogênio/metabolismo , Reação em Cadeia da Polimerase em Tempo RealRESUMO
The time courses for production of fungal biomass, lipid, phenolic and arachidonic acid (ARA) as well as expression of the genes involved in biosynthesis of ARA and lipid were examined in Mortierella alpina CBS 754.68. A significant increase in the arachidonic acid content in lipids that coincided with reduced levels of lipid was obtained. Reduced gene expression occurred presumably due to the steady reduction of carbon and nitrogen resources. However, these energy resources were inefficiently compensated by the breakdown of the accumulated lipids that in turn, induced up-regulated expression of the candidate genes. The results further indicated that the expression of the GLELO encoding gene is a rate-limiting step in the biosynthesis of ARA in the early growth phase.