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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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Citations
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Journal Article
TL;DR: In this paper, a proximate analysis of local rice bran and brown rice disclosed a distinguish level of chemical compositions, including lipid, carbohydrate, and ash, in brown rice.
Abstract: A proximate analysis study of local rice bran and brown rice disclosed a distinguish level of chemical compositions. Lipid, carbohydrate and ash occupy in rice bran, while fibre is a predominant component in brown rice. Both perceptible anti-cholesterol substrates were grown with locally isolated Fusarium pseudocircinatum IBRL B3-4 to obtain the best lovastatin activity via dichloromethane extraction. Evaluation of lovastatin production at different substrate thickness ranges of 0.25 to 1.5 cm in a static tray system (20x20x6 cm 3 ) exposed the highest production at 0.5 cm level (1135.0±6.7 µg/g dry solid of lovastatin). Meanwhile, effects of physical parameters investigation interpreted that the original substrate size, 60% (v/w) moisture content and ambient local temperature of 30±2°C as the most suitable conditions to generate lovastatin at the utmost level. Meanwhile, the maximum production was synthesized at day 12 th (twelfth) under solid substrate fermentation system. A significant activity increment was revealed after 60 % (v/v) moisture content had been applied into tray system. In more specific, it boosted up to 2271.7±14.4 µg/g dry solid of lovastatin.

2 citations

Journal ArticleDOI
TL;DR: Thin layer chromatography, Fourier Transform Infrared spectroscopy analysis confirmed the presence of lovastatin in the sample produced by A. terreus NCIM 657 and it was observed that glucose as a sole carbon source resulted in diminished production of Lovastatin as compared to cases where other carbon sources were supplemented in medium along with glucose.
Abstract: Lovastatin is a natural secondary metabolite produced by Aspergillus terreus. Optimization of different process parameters like pH of medium, incubation period and selection of different carbon sources etc. was investigated for maximum production of lovastatin using Aspergillus terreus NCIM 657. The kinetics of lovastatin production was also investigated up to fourteen days of production under batch mode. It was found that a temperature of 28 ?C for incubation, a medium pH 6.5 and an agitation speed of 180rpm for seven days yielded maximum concentration of lovastatin. It was also observed that glucose as a sole carbon source resulted in diminished production of lovastatin as compared to cases where other carbon sources were supplemented in medium along with glucose. Thin layer chromatography, Fourier Transform Infrared spectroscopy analysis confirmed the presence of lovastatin in the sample produced by A. terreus NCIM 657

2 citations

Book ChapterDOI
01 Jan 2020

2 citations

25 Feb 2015
TL;DR: Resumen es: Los medios de cultivo constituyen el micromundo de los microorganismos en condiciones de laboratorio, intentando simular su habitat natural en relacion with el cultivo.
Abstract: Los medios de cultivo constituyen el micromundo de los microorganismos en condiciones de laboratorio, intentando simular su habitat natural en relacion con la satisfaccion de sus mas vitales necesidades como ser vivo. El diseno de un medio de cultivo responde a las exigencias del microorganismo en cuestion y a la finalidad que se persigue con su multiplicacion; por tanto, la seleccion y la concentracion adecuada de los nutrientes es un factor de vital importancia. Sin embargo, el empleo de una apropiada metodologia es lo que hace posible la obtencion de un medio de cultivo optimo, ya sea para el crecimiento y/o la produccion de metabolitos por parte del microorganismo. Existen numerosos metodos y disenos de optimizacion con disimiles caracteristicas, ventajas y limitaciones que determinan su empleo en las diversas ramas de la investigacion. Se abordaron en el trabajo los disenos factoriales completos y fraccionados, el Plackett Burman, el Box-Behnkeny el uniforme. La optimizacion de los componentes del medio y de las condiciones ambientales garantiza notables incrementos en los rendimientos de los procesos fermentativos de formarapida y economica. Por tanto, esta revision pretende abordar los principios y metodos de optimizacion, asi como caracterizar y ejemplificar la aplicacion de los disenos mas usados en la optimizacion de medios de cultivos, con el fin de extender su uso a la biotecnologia agricola.

1 citations


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

  • ...Las condiciones de fermentación optimizadas elevaron los títulos de producción cuatro veces, en comparación con la peor de las combinaciones estudiadas (15)....

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  • ...Este diseño es muy similar en idea al Compuesto Central, solo que difiere en que no son usados los puntos esquinas o extremos y usa solo tres niveles (15)....

    [...]

Book ChapterDOI
01 Jan 2021
TL;DR: This review attempts to elucidate all aspects of lovastatin biosynthesis ranging from various screening methods tested in isolating high-lovastatin yielding fungal strains to high-end biosimulation methodologies to enhance its overall yield.
Abstract: The filamentous fungi such as Aspergillus terreus, Aspergillus flavus, Monascus ruber, and Monascus purpureus have been well reported to produce a proven anticholesterol drug, lovastatin. Lovastatin (mevinolin) is a naturally occurring polyketide secondary metabolite present in the Chinese fermented red yeast rice known as angkak or red rice koji. In the year 1987, FDA (Food and Drug Administration, USA) approved lovastatin as a drug for the treatment of hypercholesterolemia. Since then it is considered as a medicinally and industrially important secondary metabolite. Various fermentation methods, i.e., Liquid surface (LSF), Submerged (SmF), and Solid-State (SSF) fermentation, employing Aspergillus terreus and A. flavus cultures are commercially used for lovastatin biosynthesis. The yield of lovastatin from the said fungal strains is generally reported to be low, thus making room for further investigation on increasing its yield by applying new scientific tools. The literature review indicates recent studies of applying newer standard methods, namely Plackett–Burman Design (PBD), Response Surface Methodology (RSM), and hybrid of Artificial Neural Network and Genetic Algorithm (ANN-GA) for the optimization of various nutrients and process parameters for the biosynthesis of lovastatin. This review attempts to elucidate all aspects of lovastatin biosynthesis ranging from various screening methods tested in isolating high-lovastatin yielding fungal strains to high-end biosimulation methodologies to enhance its overall yield.

1 citations

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