Mutants of a lovastatin-hyperproducingAspergillus terreus deficient in the production of sulochrin

Vinci, Victor A.; Hoerner, T. D.; Coffman, Allen D.; Schimmel, T. G.; Dabora, R. L.; Kirpekar, A. C.; Ruby, Carolyn L.; Stieber, R. W.

doi:10.1007/bf01578762

Cited by 52 publications

(16 citation statements)

References 13 publications

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“…Nevertheless, such a microorganism of the rich secondary metabolism as A. terreus is also capable of biosynthesis of other compound, such as sulochrin [10]. This compound is also a product of the polyketide synthase (PKS) pathway [11] and, as mevinolinic acid, is formed from malonyl-CoA and acetyl-CoA [4].…”

Section: Introductionmentioning

confidence: 99%

“…This compound is also a product of the polyketide synthase (PKS) pathway [11] and, as mevinolinic acid, is formed from malonyl-CoA and acetyl-CoA [4]. For the purpose of lovastatin production, sulochrin is considered as an unwanted co-metabolite due to the toxicities associated with the contaminants and/or due to difficulties in removing the contaminants during downstream processing [10].…”

Section: Introductionmentioning

confidence: 99%

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PRODUCTION OF LOVASTATIN AND SULOCHRIN BY Aspergillus terreus USING SOLID STATE FERMENTATION

Dewi

Artanti

Mulyani

et al. 2011

MST

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Lovastatin is an anti-cholesterol agent that was produced by Aspergillus terreus using solid state fermentation (SSF). During this fermentation process, sulochrin is also produced as an unwanted co-metabolite. However, our previous result showed that sulochrin had potential as antidiabetes because it is an inhibitor agent of α-glucosidase. In this paper, we reported our observation on lovastatin and sulochrin production pattern in relation with inhibitor α-glucosidase activity during eleven days fermentation of A. terreus koji (SSF) ethyl acetate extract. Koji obtained from solid state fermentation with rice as the substrate and incubated at room temperature, sample is taken daily for eleven day (D-1 to D-11). Lovastatin and sulochrin production was measured by Liquid Chromatography-Mass Spectrometer based on their molecular weight m/z 404.5 and 332.3 respectively. The inibitory activity is measured by inhibition model of koji extract against α-glucosidase (EC 3.2.1.20) from Saccharomyces cereviceae. The results show that lovastatin production was started on the day 2 (0.04 mg/g) and achieving the optimal production on day 7 (11.46 mg/g), while sulochrin production was started on day 4 (0.60 mg/g) and keep produced until the end of fermentation period at Day 11 (3.11 mg/g). Koji extract was started to show inhibitory to α-glucosidase activity on Day 5 (IC 50 = 23.34 µg/mL) and keep showed activity until Day 11 (IC 50 =3.33 µg/mL). These results suggest that inhibitory activity of koji extract to α-glucosidase activity have relation with sulochrin biosynthesis production.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

PRODUCTION OF LOVASTATIN AND SULOCHRIN BY Aspergillus terreus USING SOLID STATE FERMENTATION

Dewi

Artanti

Mulyani

et al. 2011

MST

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“…This was accomplished with the lovastatin process of Aspergillus terreus, which included production of two other polyketides, sulochrin and asterric acid, along with lovastatin. Both undesirable products were eliminated by mutation [51]. Such a manipulation is much less costly than the removal of coproducts during downstream processing.…”

Section: Laboratory Fermentation Improvementmentioning

confidence: 99%

From natural products discovery to commercialization: a success story

Demain

2006

J IND MICROBIOL BIOTECHNOL

116

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In order for a natural product to become a commercial reality, laboratory improvement of its production process is a necessity since titers produced by wild strains could never compete with the power of synthetic chemistry. Strain improvement by mutagenesis has been a major success. It has mainly been carried out by "brute force" screening or selection, but modern genetic technologies have entered the scene in recent years. For every new strain developed genetically, there is further opportunity to raise titers by medium modifications. Of major interest has been the nutritional control by induction, as well as inhibition and repression by sources of carbon, nitrogen, phosphate and end products. Both strain improvement and nutritional modification contribute to the new process, which is then scaled up by biochemical engineers into pilot scale and later into factory size fermentors.

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“…Random mutation and selection strategies have been reported for obtaining overproducing isolates of A. terreus (Vinci et al 1991). A particularly useful rapid screening method for identifying lovastatin overproducers was described by Kumar et al (2000b).…”

Section: Introductionmentioning

confidence: 99%

Rapid screening of Aspergillus terreus mutants for overproduction of lovastatin

Ferron

López

Pérez

et al. 2005

World J Microbiol Biotechnol

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SummaryA novel rapid screening method is demonstrated for isolating lovastatin-overproducing strains of Aspergillus terreus. The screening methodology, based on the activity of lovastatin against the yeast Candida albicans, is nearly three times as fast as the selection methods used earlier. The new 6-h assay shows a linear correlation between the quantity of lovastatin generated by A. terreus isolates and the inhibition zones obtained on plates of C. albicans. The new technique is less expensive and requires less labour.

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Mutants of a lovastatin-hyperproducingAspergillus terreus deficient in the production of sulochrin

Cited by 52 publications

References 13 publications

PRODUCTION OF LOVASTATIN AND SULOCHRIN BY Aspergillus terreus USING SOLID STATE FERMENTATION

PRODUCTION OF LOVASTATIN AND SULOCHRIN BY Aspergillus terreus USING SOLID STATE FERMENTATION

From natural products discovery to commercialization: a success story

Rapid screening of Aspergillus terreus mutants for overproduction of lovastatin

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