Biosynthesis and biotechnological production of statins by filamentous fungi and application of these cholesterol-lowering drugs

Rollini, M. Manzoni, M.

doi:10.1007/s00253-002-0932-9

Cited by 410Microbial Natural Products and BiosynthesisSteroid Chemistry and BiochemistryCancer, Lipids, and Metabolism

Biosynthesis and biotechnological production of statins by filamentous fungi and application of these cholesterol-lowering drugs

Rollini, M. Manzoni, M.·2002·Applied Microbiology and Biotechnology

DOI 10.1007/s00253-002-0932-9

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Abstract

Hypercholesterolemia is considered an important risk factor in coronary artery disease. Thus the possibility of controlling de novo synthesis of endogenous cholesterol, which is nearly two-thirds of total body cholesterol, represents an effective way of lowering plasma cholesterol levels. Statins, fungal secondary metabolites, selectively inhibit hydroxymethyl glutaryl-coenzyme A (HMG-CoA) reductase, the first enzyme in cholesterol biosynthesis. The mechanism involved in controlling plasma cholesterol levels is the reversible inhibition of HMG-CoA reductase by statins, related to the structural similarity of the acid form of the statins to HMG-CoA, the natural substrate of the enzymatic reaction. Currently there are five statins in clinical use. Lovastatin and pravastatin (mevastatin derived) are natural statins of fungal origin, while symvastatin is a semi-synthetic lovastatin derivative. Atorvastatin and fluvastatin are fully synthetic statins, derived from mevalonate and pyridine, respectively. In addition to the principal natural statins, several related compounds, monacolins and dihydromonacolins, isolated fungal intermediate metabolites, have also been characterized. All natural statins possess a common polyketide portion, a hydroxy-hexahydro naphthalene ring system, to which different side chains are linked. The biosynthetic pathway involved in statin production, starting from acetate units linked to each other in head-to-tail fashion to form polyketide chains, has been elucidated by both early biogenetic investigations and recent advances in gene studies. Natural statins can be obtained from different genera and species of filamentous fungi. Lovastatin is mainly produced by Aspergillus terreus strains, and mevastatin by Penicillium citrinum. Pravastatin can be obtained by the biotransformation of mevastatin by Streptomyces carbophilus and simvastatin by a semi-synthetic process, involving the chemical modification of the lovastatin side chain. The hypocholesterolemic effect of statins lies in the reduction of the very low-density lipoproteins (VLDL) and LDL involved in the translocation of cholesterol, and in the increase in the high-density lipoproteins (HDL), with a subsequent reduction of the LDL- to HDL-cholesterol ratio, the best predictor of atherogenic risk. The use of statins can lead to a reduction in coronary events related to hypercholesterolemia, but the relationship between benefit and risk, and any possible interaction with other drugs, must be taken into account.

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Statins are competitive inhibitors of HMG-CoA reductase, the key enzyme catalyzing the rate-limiting step of sterol biosynthesis.
“Statins are competitive inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the key enzyme which catalyzes the rate limiting step of sterols biosynthesis.24”
From Synergistic antifungal activity of statin–azole associations as witnessed by Saccharomyces cerevisiae- and Candida utilis-bioassays and ergosterol quantification (2013) · cites this paper as [24]

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Authors: Rollini, M. M.
Venue: Applied Microbiology and Biotechnology
Publisher: Springer Science and Business Media LLC
Published: 2002-04-01
Volume: 58
Issue: 5
Pages: 555-564
ISSN: 0175-7598 (ISSN-L)
1432-0614
DOI: 10.1007/s00253-002-0932-9
OpenAlex: W2156125238
Cited by: 410
References: 77
Citations by year: 2026: 8 · 2025: 15 · 2024: 15 · 2023: 22 · 2022: 22 · 2021: 12 · 2020: 32 · 2019: 23 · 2018: 16 · 2017: 13 · 2016: 22 · 2015: 20 · 2014: 16 · 2013: 23 · 2012: 29
FWCI: 4.22
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Applied Microbiology and Biotechnology (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Pharmacology › Microbial Natural Products and Biosynthesis
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Steroid Chemistry and Biochemistry
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
Keywords: statins, fungal secondary metabolites, polyketide biosynthesis, HMG-CoA reductase inhibition, cholesterol biosynthesis, hypercholesterolemia, lovastatin, mevastatin, pravastatin, simvastatin, aspergillic acid, monacolins, Aspergillus terreus, Penicillium citrinum, biotransformation, cholesterol-lowering drugs
MeSH terms: Biotechnology, Fungi, Models, Chemical, Hydroxymethylglutaryl-CoA Reductase Inhibitors

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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

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Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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Biosynthesis and biotechnological production of statins by filamentous fungi and application of these cholesterol-lowering drugs

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