• KSBB Journal
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• v.16 no.1
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• pp.87-94
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• 2001

The biosynthesis of Lovastatin, a cholesterol lowering agent formed by the filamentous fungus, cerulenin-resistant Aspergillus terreus mutant was studied in shake flasks and bioreactors. The lovastatin production could be improved by fed-batch under the limited condition of carbon source. The relationship between the fungal morphology and the lovastatin production was also examined during the fed-batch cultures. The fed-batch studies in shake flasks were carried out to find the optimum glucose feeding method, and the pulsed feeding of glucose from 3 days onward at 24 hours intervals was found to be optimal to increase the lovastatin production and reduce the average pellet size. When the pH was controlled at around 5.8 during the whole fermentation period, the lovastatin concentration reached 384 mg/L, which is much higher than the values obtained pH-uncontrolled and pH 7.4. The optimal glucose feeding strategies was found that 30 g/L of glucose was added initially in batch mode, and then fed-batch was conducted by continuous addition of glucose solution(180 g/L) from 72 to 240 hr at a rate of 1.2 mL/hr at $28^{\circ}C$, pH 5.8, 400 rpm, and 1.0 vvm. The lovastatin concentration of 547 mg/L was obtained in 168 hr. It was about 1.5 times higher than the value of the batch fermentation.

• KSBB Journal
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• v.14 no.1
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• pp.36-44
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• 1999

The biosynthesis of Lovastatin, a cholesterol lowering agent formed by the filamentous fungus Aspergillus terreus, was investigated in shaking flask. The effects of essential elements in the experimental medium such as carbon, nitrogen, phosphate sources, and amino acids were examined to increase Lovastatin productivity. Lovastatin production in shaking flasks was 68 mg/L in the used medium. Effect of carbon source on Lovastatin production was performed. As a carbon source in the medium, 45 mL/L of glycerol increased the Lovastatin production up to 256 mg/L, which was found to be improved almost 3.5 times in comparison with that in common medium. The optimum concventration of peptonized milk as nitrogen source was obtained 30g/L on Lovastatin production. The severe inhibition of the cell growth and the Lovastatin production were observed in shaking flasks conducted at the medium contained ammonium carbonate as a nitrogen source. Lovastatin production various concentrations of several phosphate compounds was also examined. The addition of either potassium phosphate diabsic or sodium phosphate dibasic increased the Lovastatin production and the optimal level of potassium phosphate dibasic was 6 g/L. Even though Lovastatin contain methionine-derived methyl group, L-methionine and DL-methionine tend to diminish the Lovastatin production. Among the amino acids, L-histidine and L-tryptophan had a remarkable enhancing effect on the Lovastatin production. The optimal concentration of L-histidine and L-tryptophan was 6g/L.

• Microbiology and Biotechnology Letters
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• v.32 no.1
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• pp.52-59
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• 2004

When both fructose and galactose were added to a production medium as carbon sources, the productivity of PAFS (Psedomonas Antifungal Substance) biosynthesized by Pseudomonas aeruginosa was observed to be reduced significantly due to the well-known phenomenon of catabolite repression. In order to overcome this phenomenon by use of fermentation bioprocess, fed-batch cultivation method was examined. In addition, a high producer mutant strain, AP-20 obtained by a rational screening method was tested for its productivity of PAFS in both batch and fed-batch fermentation processes. Notably fed-batch operation showed approximately 4 fold higher PAFS productivity than traditional batch operation process. It was appeared that galactose was utilized principally for the cell growth of Pseudomonas aeruginosa whereas large portion of fructose was used for the biosynthesis of PAFS. Furthermore it was observed that composition and feeding rate of production media should be optimized even in the fed-batch fermentation bioprocess. As an example, very slow feeding of carbon sources gave rather negative effect on the production of PAFS due to significant limitation of carbon and energy sources available for the producer microorganism.

• Journal of the Korean Society of Food Science and Nutrition
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• v.37 no.5
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• pp.666-670
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• 2008

Lovastatin (Mevinolin, Monacolin K) is a well-known drug for the therapy of hypercholesterolemia. It is an important fungal secondary metabolite as it inhibits 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase, EC 1.1.1.34) which catalyzes a major rate-limiting step in the biosynthesis of cholesterol. Both soybeans and black soybeans with Aspergillus terreus ATCC 20542 mutant were used as the seed culture for the mass production of lovastatin. The production of lovastatin in soybean seed culture of Asp. terreus was twofold compared to that of black soybean seed culture. The effect of two different vessels (petri dish and Erlenmeyer flask) on lovastatin production was also studied. The production of lovastatin on petri dish was tenfold to that of Erlenmeyer flask. Furthermore, the most lovastatin production on rice bran was achieved when the soybean seed culture was treated by heat shock at $30^{\circ}C$ for 1 hour, representing 82% of HMG-CoA reductase inhibition in the koji extract. We estimated that the heat treated soybean seed culture could be a new method for the mass production of lovastatin.

• Journal of Applied Biological Chemistry
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• v.61 no.1
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• pp.83-91
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• 2018

Advances in bacterial and fungal genome mining uncover a plethora of cryptic secondary metabolite biosynthetic gene clusters. Guided by the genome information, targeted transcriptional derepression could be employed to determine the product of a cryptic gene cluster and to explore its biological role. Monascus spp. are food grade filamentous fungi popular in eastern Asia and several genome data belong to them are now available. We achieved transcription activation of a cryptic fungal polyketide synthase-nonribosomal peptide synthase gene Mpfus1 in Monascus purpureus ${\Delta}MpPKS5$ by inserting Aspergillus gpdA promoter at the upstream of Mpfus1 through double crossover gene replacement. The gene cluster with Mpfus1 show a high similarity to those for the biosynthesis of conjugated polyene derivatives with 2-pyrrolidone ring and the mycotoxin fusarin is the representative member of this group. The ${\Delta}MpPKS5$ is incapable of producing azaphilone pigment, providing an excellent background to identify chromogenic and UV-absorbing compounds. Activation of Mpfus1 resulted in a yellow hue on mycelia and its methanol extract exhibit a maximum absorption at 365 nm. HPLC analysis of the organic extracts indicated the presence of a variety of yellow compounds in the extract. This implies that the product of MpFus1 is metabolically or chemically unstable. LC-MS analysis guided us to predict the MpFus1 product and to propose that the Mpfus1-containing gene cluster encode the biosynthesis of a desmethyl analogue of fusarin. This study showcases the genome mining in Monascus and the possibility to unveil new biological activities embedded in it.