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Journal ArticleDOI

Fermentation optimization for the production of lovastatin by Aspergillus terreus: use of response surface methodology

TL;DR: A Box-Behnken experimental design was used to investigate the effects of five factors (oxygen content in the gas phase, concentrations of C, N and P, and fermentation time) on the concentrations of biomass and lovastatin produced in batch cultures of Aspergillus terreus as discussed by the authors.
Abstract: A Box-Behnken experimental design was used to investigate the effects of five factors—ie oxygen content in the gas phase; concentrations of C, N and P; and fermentation time—on the concentrations of biomass and lovastatin produced in batch cultures of Aspergillus terreus. The values of the various factors in the experiment ranged widely, as follows: 20-80% (v/v) oxygen in the aeration gas; 8-48 g dm −3 C-concentration; 0.2-0.6 g dm −3 N-concentration; 0.5-2.5 g dm −3 phosphate-concentration; and 7-11 days fermentation time. No previous work has used statistical analysis in documenting the interactions between oxygen supply and nutrient concentrations in lovastatin production. The Box-Behnken design identified the oxygen content in the gas phase as the principal factor influencing the production of lovastatin. Both a limitation and excess of oxygen reduced lovastatin titers. A medium containing 48 g dm −3 C supplied as lactose, 0.46 g dm −3 N supplied as soybean meal, and 0.79 g dm −3 phosphate supplied as KH2PO4, was shown to support high titers (∼230 mg dm −3 )o f lovastatin in a7 -day fermentation in oxygen-rich conditions (80% v/v oxygen in the aeration gas). Under these conditions, the culture medium had excess carbon but limiting amounts of nitrogen. The optimized fermentation conditions raised the lovastatin titer by four-fold compared with the worst-case scenario within the range of factors investigated.  2004 Society of Chemical Industry

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Dissertation
04 Nov 2016
TL;DR: Las mejores condiciones de produccion del pigmento fueron pH 8, medio caldo papa y dextrosa, y luz blanca continua, y se observo un efecto fungicida contra los hongos fitopatogenos.
Abstract: El objetivo de este trabajo fue producir extractos crudos de dos aislamientos (H1 y H2) de P. sanguineus y evaluar su efecto en el control in vitro de hongos y bacterias fitopatogenas de frutas y hortalizas en postcosecha asi como de interes clinico. Se determinaron las mejores condiciones de produccion del pigmento naranja del hongo. Para esto se realizo un diseno experimental completamente al azar en arreglo factorial en donde los factores y niveles fueron: pH (8.0, 8.5 y 9.0), medio de cultivo liquido (caldo de papa y dextrosa, y extracto de malta) y tipo de luz (normal y blanca continua). El pigmento naranja se extrajo con acetato de etilo. El pigmento se concentro y se utilizo en el control de los hongos (Colletotrichum fragariae, C. gloeosporioides y Botrytis cinerea) y las bacterias (Erwinia amylovar y Pectobacterium carotovorum) en postcosecha; asi como de bacterias de interes clinico (Salmonella typhi, Bacillus cereus, Escherichia coli, Staphylococcus aureus, Bacillus subtilis, Staphylococcus aureus, Enterobacter agglomerans, Shigella dysenteriae, Klebsiella rhinoescleromatis, Yersinia enterocolitica y K. pneumoniae). Las mejores condiciones de produccion del pigmento fueron pH 8, medio caldo papa y dextrosa, y luz blanca continua. Se observo un efecto fungicida contra los hongos fitopatogenos, obteniendose una reduccion del 70 y 60 % del crecimiento de B. cinerea con la adicion de 10, y 20 mg/mL del extracto crudo del pigmento de P. sanguineus, respectivamente. Para C. fragarie, la inhibicion fue mayor al 50% y solo del 40% para C. gloeosporioides. En el caso de las bacterias fitopatogenas, se determino la concentracion minima inhibitoria para: E. amylovora (H1>12mg/mL; H2, 7mg/mL) y P. carotovorum (H1, 10mg/mL; H2, >12mg/mL); asi como para las bacterias de interes clinico: Salmonella typhi (8mg/mL), Bacillus cereus (H1, 8mg/mL; H2,10mg/mL), Klebsiella pneumoniae (>12mg/mL) y Shigella dysenteriae (8mg/mL).
01 Jan 2009
TL;DR: In this paper, an integrated approach to the development of a potential active pharmaceutical ingredient, eritadenine, a cholesterol reducing compound originating from the shiitake, was presented.
Abstract: The present thesis demonstrates an integrated approach to the development of a potential active pharmaceutical ingredient, eritadenine, a cholesterol reducing compound originating from the shiitake ...

Cites background from "Fermentation optimization for the p..."

  • ...1) (23, 24), which catalyses the hydrolysis of S-adenosyl-L-homocysteine to form adenosine and homocysteine (Figure 4)....

    [...]

01 Jan 2007
TL;DR: A large number of patients with high blood cholesterol levels are diagnosed with atypical central giant cell granuloma, a leading cause of death in women, and the use of statin drugs to treat such diseases is recommended.
Abstract: Cardiovascular diseases are among the main causes of death in our society and there is a strong correlation between enhanced blood cholesterol levels and the development of such diseases. The popul ...

Cites background from "Fermentation optimization for the p..."

  • ...Another anti-tumour active polysaccharide, KS-2, has been isolated from shiitake mycelia (LEM) (19)....

    [...]

01 Jan 2015
TL;DR: In this article, the authors optimized the culture medium and fermentation conditions by using single factor experiment and response surface method (Box-Behnken) to improve the yield of itaconic acid in the fermentation process.
Abstract: Itaconic acid is an important biochemical product and widely used in chemical intermediate. In order to improve the yield of itaconic acid in the fermentation process, we optimized the culture medium and fermentation conditions by using single factor experiment and response surface method (Box-Behnken). The results showed that the optimal medium compositions for itaconic acid production were as follows: glucose, NH4NO3, MgSO4, KH2PO4, FeSO4, ZnSO4, corn steep liquor were 120 g/L, 2.5 g/L, 1.9 g/L,0.2 g/L, 0.2 g/L, 0.15 g/L and 2 g/L respectively. The optimum fermentation conditions through single factor experiments were found to be a temperature of 32 0 C, initial pH of 2.5, rotation speed of 200 r/min and shake flask liquid volume of 60mL/250mL leading to the itaconic acid yield of 42.71±0.24 g/L. Then fermented in the stirred tank with a ventilation volume of 4.0 L/m, rotation rate of 500 r/min, fermentation period was 144 hours leading to the itaconic acid yield of 53.63±0.21 g/L. Thus, by fermentation processing optimization, the yield of itaconic acid was raised effectively.
01 Jan 2013
TL;DR: Good potential for valorisation of biodiesel-derived glycerol via biochemical routes to value-added statin drugs is suggested, following research on lovastatin production and biomass yield of A. terreus ATCC 20542.
Abstract: Aspergillus terreus ATCC 20542 is an important fungus for lovastatin production, a cholesterol-lowering drug. In this research, we attempted to produce lovastatin using the fungus, with crude glycerol as an inexpensive carbon source and a biodiesel industry-derived waste product. The effect of varying concentrations of crude glycerol (10 g/L, 30 g/L and 50 g/L), incubation periods (2, 4, 6, 8, 10 and 12 days), nitrogen sources (ammonium sulfate, yeast extract and soya waste) and nitrogen source concentrations (4 g/L, 8 g/L and 12 g/L) were tested on lovastatin production and biomass yield of A. terreus ATCC 20542. Pure glycerol with a concentration of 30 g/L along with 4 g/L of yeast extract was used in control experiments. The highest lovastatin concentration, which was 6.7 mg/L, was obtained in the culture amended with 10 g/L crude glycerol concentration. This value is 60% higher than the value obtained in the culture with 50 g/L crude glycerol (4.2 mg/L). In the presence of 4 g/L soya waste, the 7-day old fungal culture produced 5.9 mg/L, which was about 300% higher than the yield in yeast extract-amended culture. These results suggest good potential for valorisation of biodiesel-derived glycerol via biochemical routes to value-added statin drugs.
References
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Journal ArticleDOI
TL;DR: In this paper, a class of incomplete three level factorial designs useful for estimating the coefficients in a second degree graduating polynomial are described and the designs either meet, or approximately meet, the criterion of rotatability and for the most part can be orthogonally blocked.
Abstract: A class of incomplete three level factorial designs useful for estimating the coefficients in a second degree graduating polynomial are described. The designs either meet, or approximately meet, the criterion of rotatability and for the most part can be orthogonally blocked. A fully worked example is included.

3,194 citations

Journal ArticleDOI
TL;DR: It was shown that mevinolin was an orally active cholesterol-lowering agent in the dog and orally administered sodium mevinolinate was an active inhibitor of cholesterol synthesis in an acute assay.
Abstract: Mevinolin, a fungal metabolite, was isolated from cultures of Aspergillus terreus. The structure and absolute configuration of mevinolini and its open acid form, mevinolinic acid, were determined by a combination of physical techniques. Mevinolin was shown to be 1,2,6,7,8,8a-hexahydro-beta, delta-dihydroxy-2,6-dimethyl-8-(2-methyl-1-oxobutoxy)-1-naphthalene-hepatanoic acid delta-lactone. Mevinolin in the hydroxy-acid form, mevinolinic acid, is a potent competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase [mevalonate: NADP+ oxidoreductase (CoA-acylating), EC 1.1.1.34]; its Ki of 0.6 nM can be compared to 1.4 nM for the hydroxy acid form of the previously described related inhibitor, ML-236B (compactin, 6-demethylmevinolin). In the rat, orally administered sodium mevinolinate was an active inhibitor of cholesterol synthesis in an acute assay (50% inhibitory dose = 46 microgram/kg). Furthermore, it was shown that mevinolin was an orally active cholesterol-lowering agent in the dog. Treatment of dogs for 3 weeks with mevinolin at 8 mg/kg per day resulted in a 29.3 +/- 2.5% lowering of plasma cholesterol.

1,517 citations

Journal ArticleDOI
TL;DR: The experiments reported in this paper demonstrate that MG236A and ML-236B inhibit specifically 3-hydroxy-3-methylglutaryl (HMG)CoA reductase (EC 1 .I .1.34), the rate-limiting enzyme in cholesterol synthetic pathway, without affecting the rest of the enzymes involved in this pathway, and that the inhibition is competitive with respect to the substrate HMG-CoA.

699 citations

Journal ArticleDOI
TL;DR: This review deals with polyketides produced by the filamentous fungusMonascus which include: 1) a group of yellow, orange and red pigments, 2) agroup of antihypercholesterolemic agents including mevinolin and related compounds and 3) the newly discovered metabolite ankalactone.
Abstract: This review deals with polyketides produced by the filamentous fungusMonascus which include: 1) a group of yellow, orange and red pigments, 2) a group of antihypercholesterolemic agents including mevinolin and related compounds and 3) the newly discovered metabolite ankalactone. Biosynthesis, methods of production, isolation and biological activities of these secondary metabolites are discussed.

359 citations