Uric acid in plants and microorganisms: Biological applications and genetics - A review.

Uric acid increased accumulation and/or reduced excretion in human bodies is closely related to pathogenesis of gout and hyperuricemia. It is highly affected by the high intake of food rich in purine. Uric acid is present in both higher plants and microorganisms with species dependent concentration. Urate-degrading enzymes are found both in plants and microorganisms but the mechanisms by which plant degrade uric acid was found to be different among them. Higher plants produce various metabolites which could inhibit xanthine oxidase and xanthine oxidoreductase, so prohibit the oxidation of hypoxanthine to xanthine then to uric acid in the purine metabolism. However, microorganisms produce group of degrading enzymes uricase, allantoinase, allantoicase and urease, which catalyze the degradation of uric acid to the ammonia. In humans, researchers found that several mutations caused a pseudogenization (silencing) of the uricase gene in ancestral apes which exist as an insoluble crystalloid in peroxisomes. This is in contrast to microorganisms in which uricases are soluble and exist either in cytoplasm or peroxisomes. Moreover, many recombinant uricases with higher activity than the wild type uricases could be induced successfully in many microorganisms. The present review deals with the occurrence of uric acid in plants and other organisms specially microorganisms in addition to the mechanisms by which plant extracts, metabolites and enzymes could reduce uric acid in blood. The genetic and genes encoding for uric acid in plants and microorganisms are also presented.

High expression level of antioxidants and pharmaceutical bioactivities of endophytic fungus Chaetomium globosum JN711454.

In order to maximize antioxidant activity of pharmaceutical bioactive endophytic fungus Chaetomium globosum JN711454 during fermentation process, designed fermentation experiments of culture media for three levels of eight culture factors were performed using a Taguchi orthogonal array (OA) design with layout L18 (2(1) × 3(7)). The agitation and the potato extract were the most significant affecting factors, and their interaction contributed significantly to fungus activity. The production of antioxidants was more favorable for static condition with 25 g potato extract/100 m. The remaining factors had no strong impact when considered individually. The validation of statistically optimized medium indicated the improvement of antioxidant activity to a level of twofold with approximately overall 40% enhancement in activity. The extract of optimized medium was investigated for various pharmaceutical bioactivities; it revealed a moderate antimicrobial activity, strong anticancer activity against HepG-2, UACC62 cell lines, an antiviral activity against HSV-2 virus, and strong inhibitory activity to butyrylcholinesterase enzyme, one of the neurohydrolase enzymes that play a major role in development of Alzheimer's disease. As a result of applying statistical fermentation designs, the optimized conditions of endophytic fungus C. globosum JN711454 developed a cost-effective production medium by using inexpensive commercial potato extracts statically, which can lower the energy requirement and could become an efficient, economic, and viable fermentation process for production of pharmaceutical secondary metabolites.

Biological evaluation of endophytic fungus, Chaetomium globosum JN711454, as potential candidate for improving drug discovery.

The main objective of this research work focused on investigating the biological and chemical aspects of endophytic fungus Chaetomium globosum, for pharmaceutical purposes to improve the drug discovery process. The endophytic C. globosum was isolated from healthy leaves of Egyptian medicinal plant Adiantum capillus-veneris collected from Saint Katherine Protectorate, Sinai, Egypt. The identification of C. globosum was on the basis of classical and molecular taxonomy. Gene encoding for 18S rRNA was partially sequenced, submitted to the GenBank and got the accession number JN711454, to resolve the phylogenetic relations with fungal ancestor using phylogenetic tree. To explore the biosynthetic power of endophytic C. globosum JN711454, the fungus was cultivated over five different media, oatmeal, rice, yeast malt glucose, potato dextrose agar (PDA) and Czapek's dox media, for 3 weeks at 30 °C, followed by extraction with different solvents, ethyl acetate (EA), and methanol. The ethyl acetate extract of C. globosum cultivated on PDA medium was the most potent extract. It showed strong antioxidant activity with EC50 11.5 µg/ml, potent anticancer activity with 55 % toxicity toward HepG-2 cells at 100 µg/ml and 66 % cytotoxicity to FGC4 cells at 250 µg/ml, promising butyrylcholinesterase inhibitory activities (>85 %), and moderate antimicrobial and stopped the attachment of HSV-2 virus to VERO cells. The metabolomic profiling of PDA-EA extract using LC-MS revealed the presence of several metabolites to which the observed bioactivities could be attributed. Here we report for the first time inhibitory activity of endophytic C. globosum JN711454 secondary metabolites to butyrylcholinesterase, one of neuro hydrolase enzymes that play a major role in development of Alzheimer's disease.