Biosynthesis of the hypocholesterolemic agent mevinolin by Aspergillus terreus. Determination of the origin of carbon, hydrogen, and oxygen atoms by carbon-13 NMR and mass spectrometry

Moore, Richard N.; Bigam, Glen; Chan, Jean K.; Hogg, A. M.; Nakashima, Thomas T.; Vederas, John C.

doi:10.1021/ja00298a046

Cited by 125 publications

(68 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…1) Some different types of metabolites have been subsequently isolated from A. terreus strains. [2][3][4][5][6][7][8] Among these, some sesquiterpene lactone and butyrolactone compounds have exhibited potent acetylcholinesterase inhibition activity and cyclin-dependent kinases inhibition activity.…”

mentioning

confidence: 99%

“…The crude extract of this strain exhibited cytotoxic activity in vitro against HCT-8, Bel-7402, BGC-823, and A2780 cell lines (IC 50 1.28, >50, 0.86, and 2.71 µg/mL, respectively), which spurred us further exploring new active compounds from the fungus. Herein, we describe the fermentation, isolation and characterization of new butyrolactone, 7″-hydroxybutyrolactone III (1), and three new cycloheptanetriones, terretrione A-C (2-4), together with five known compounds, butyrolactone I, 7) and diketopiperazines of cyclo(Leu-Pro), cyclo(Val-Pro), cyclo(Ile-Pro), cyclo(Phe-Pro) 9) and their biological activities.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Butyrolactone and Cycloheptanetrione from Mangrove-Associated Fungus <i>Aspergillus terreus</i>

et al. 2012

View full text Add to dashboard Cite

A new butyrolactone, 7″-hydroxybutyrolactone III (1) and three new cycloheptanetriones, terretrione A-C (2-4), together with five known compounds, butyrolactone I, cyclo(Leu-Pro), cyclo(Val-Pro), cyclo(IlePro), cyclo(Phe-Pro), were isolated from mangrove-associated marine fungus Aspergillus terreus. The structures of these compounds were elucidated on the basis of physical data analysis (NMR, high resolutionelectrospray ionization (HR-ESI)-MS), especially by 2D-NMR techniques. These compounds showed weak cytotoxicity in vitro against HCT-8, Bel-7402, BGC-823, A2780 cell lines.

show abstract

mentioning

confidence: 99%

mentioning

confidence: 99%

Butyrolactone and Cycloheptanetrione from Mangrove-Associated Fungus <i>Aspergillus terreus</i>

et al. 2012

View full text Add to dashboard Cite

show abstract

“…Lovastatin is an inhibitor of the enzyme hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase (mevalonate:NADP ϩ oxidoreductase [EC 1.1.1.34]) that catalyzes the reduction of HMG-CoA to mevalonate during synthesis of cholesterol (14,23,36). The biosynthetic pathway of lovastatin in A. terreus has been investigated by nuclear magnetic resonance and mass spectroscopy (5,26,38). These studies concluded that lovastatin is composed of two distinct polyketide chains joined through an ester linkage.…”

mentioning

confidence: 99%

Lovastatin Biosynthesis by Aspergillus terreus in a Chemically Defined Medium

Hajjaj

Niederberger

Duboc

2001

Appl Environ Microbiol

150

129

View full text Add to dashboard Cite

Lovastatin is a secondary metabolite produced by Aspergillus terreus. A chemically defined medium was developed in order to investigate the influence of carbon and nitrogen sources on lovastatin biosynthesis. Among several organic and inorganic defined nitrogen sources metabolized by A. terreus, glutamate and histidine gave the highest lovastatin biosynthesis level. For cultures on glucose and glutamate, lovastatin synthesis initiated when glucose consumption levelled off. When A. terreus was grown on lactose, lovastatin production initiated in the presence of residual lactose. Experimental results showed that carbon source starvation is required in addition to relief of glucose repression, while glutamate did not repress biosynthesis. A threefold-higher specific productivity was found with the defined medium on glucose and glutamate, compared to growth on complex medium with glucose, peptonized milk, and yeast extract.In filamentous fungi many secondary metabolites with complex chemical structure are synthesized via the polyketide pathway (15,33,37). Lovastatin, monacolin J, monacolin L, and mevastatin can be produced by Monascus ruber (7), Penicillium brevicompactum, and Aspergillus terreus (1, 36). Lovastatin is an inhibitor of the enzyme hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase (mevalonate:NADP ϩ oxidoreductase [EC 1.1.1.34]) that catalyzes the reduction of HMG-CoA to mevalonate during synthesis of cholesterol (14,23,36). The biosynthetic pathway of lovastatin in A. terreus has been investigated by nuclear magnetic resonance and mass spectroscopy (5,26,38). These studies concluded that lovastatin is composed of two distinct polyketide chains joined through an ester linkage. Proof that these two polyketides are assembled by two discrete polyketide synthases came from the cloning and partial characterization of the lovastatin biosynthetic gene cluster from A. terreus (16,18).Despite the knowledge of the genes and the enzymes involved in the biosynthetic pathway, little is known about the regulation and the physiology of lovastatin biosynthesis. Reported growth and production conditions for lovastatin are from batch fermentations performed on media with glucose and a complex nitrogen source (1,4,13,22,28). Both carbon and nitrogen sources are thought to exert complex regulation on gene expression and enzyme activities for polyketide synthesis, possibly at the level of catabolite repression or signaling due to limitation in growth rate or substrate limitation.The objective of this work was to investigate the influence of glucose and nitrogen source on the physiology of A. terreus and lovastatin production. Several carbon and nitrogen sources were tested in order to develop a chemically defined medium. The aim was to monitor biomass formation and lovastatin production in relation to the consumption pattern of carbon and nitrogen sources. We show here that although growth occurred on a large variety of substrates, the choice of nitrogen source had a major impact on lovastatin production. In addition, l...

show abstract

“…The chemical structure of lovastatin, a biosynthetic pathway for which has already been proposed, 16,17) resembles ML-236B. ML-236B, like lovastatin, would be formed from polyketide chains, one I8-carbon and one 4-carbon, derive from acetate in normal head to tail fashion.…”

Section: Discussionmentioning

confidence: 99%

Production of ML-236B, and Inhibitor of 3-Hydroxy-3-methylglutaryl CoA Reductase, byPenicillium citrinum:Improvements of Strain and Culture Conditions

Hosobuchi¹,

Shioiri²,

Ohyama³

et al. 1993

Bioscience, Biotechnology, and Biochemistry

View full text Add to dashboard Cite

Biosynthesis of the hypocholesterolemic agent mevinolin by Aspergillus terreus. Determination of the origin of carbon, hydrogen, and oxygen atoms by carbon-13 NMR and mass spectrometry

Cited by 125 publications

References 0 publications

Butyrolactone and Cycloheptanetrione from Mangrove-Associated Fungus <i>Aspergillus terreus</i>

Butyrolactone and Cycloheptanetrione from Mangrove-Associated Fungus <i>Aspergillus terreus</i>

Lovastatin Biosynthesis by Aspergillus terreus in a Chemically Defined Medium

Production of ML-236B, and Inhibitor of 3-Hydroxy-3-methylglutaryl CoA Reductase, byPenicillium citrinum:Improvements of Strain and Culture Conditions

Contact Info

Product

Resources

About