Inhibition of fatty acid synthetases by the antibiotic cerulenin

Vance, Dennis E.; Goldberg, Israel; Mitsuhashi, Osamu; Bloch, Konrad E.; Ōmura, Satoshi; Nomura, Setsuzō

doi:10.1016/0006-291x(72)90397-x

Cited by 267 publications

(169 citation statements)

References 7 publications

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“…It was the first inhibitor of fatty acid biosynthesis discovered. 101 It alkylates and inactivates the active-site nucleophylic cysteine of the ketosynthase enzyme of fatty acid synthetase by epoxide ring opening. Other properties that are desired in new antibiotics are improved pharmacological properties, ability to combat viruses and parasites and improved potency and safety.…”

Section: Antimicrobialsmentioning

confidence: 99%

Production of valuable compounds by molds and yeasts

Demain

Martens

2016

J Antibiot

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where he has contributed in a major way to the reputation of this department for many years. He also served as an Adjunct Professor at the University of Geneva. Among Julian's areas of study and accomplishment are fungal toxins including α-sarcin, chemical synthesis of triterpenes, mode of action of streptomycin and other aminoglycoside antibiotics, biochemical mechanisms of antibiotic resistance in clinical isolates of bacteria harboring resistance plasmids, their origins and evolution, secondary metabolism of microorganisms, structure and function of bacterial ribosomes, antibiotic resistance mutations in yeast ribosomes, cloning of resistance genes from an antibiotic-producing microbe, gene cloning for industrial purposes, engineering of herbicide resistance in useful crops, bleomycin-resistance gene in clinical isolates of Staphylococcus aureus and many other topics. He has been an excellent teacher, lecturing in both English and French around the world, and has organized international courses. Julian has also served on the NIH study sections, as Editor for several international journals, and was one of the founders of the journal Plasmid. We expect the impact of Julian's accomplishments to continue into the future.

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Section: Antimicrobialsmentioning

confidence: 99%

Production of valuable compounds by molds and yeasts

Demain

Martens

2016

J Antibiot

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“…To determine the selectivity of the response, a range of biochemical standards and fungicides were tested, with the results summarized in Table 4 and Figure 1C, D. Inhibitors of fatty acid biosynthesis, cerulenin (fatty acid synthase; Vance et al, 1972) and soraphen A1α (acetyl-CoA carboxylase; Vahlensieck et al, 1994; Figure 1C) as well as fenpropimorph ( Figure 1D), an inhibitor of 8 -7 -isomerase in ergosterol biosynthesis (Marcireau et al, 1990), were found to induce expression of β-galactosidase to reasonable levels compared to aculeacin A, suggesting that compounds affecting the synthesis of membrane components are also able to upregulate signalling through Pkc1 and Rlm1. However, the triazole fungicides flutriafol and epoxiconazole, which inhibit the 14-demethylase step in ergosterol biosynthesis, did not induce β-galactosidase expression under the conditions used (Table 4).…”

Section: Application To Drug Screeningmentioning

confidence: 99%

The effect of tea tree oil and antifungal agents on a reporter for yeast cell integrity signalling

Straede

Corran

Bundy

et al. 2007

Yeast

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Cell integrity in Saccharomyces cerevisiae is ensured by a rigid cell wall whose synthesis is controlled by a highly conserved MAP kinase signal transduction cascade. Stress at the cell surface is detected by a set of sensors and ultimately transmitted through this cascade to the transcription factor Rlm1, which governs expression of many genes encoding enzymes of cell wall biosynthesis. We here report on a number of versatile reporter constructs which link activation of a hybrid, Rlm1-lexA, by the MAP kinase Mpk1/Slt2 to the expression of the bacterial lacZ gene. This system was adapted to automated microwell screening and shown to be activated by a number of compounds inhibiting cell wall biosynthesis or interfering with plasma membrane function. In addition, we tested tea tree oil and two of its purified constituents (α-terpineol, terpinen-4-ol) for their effects on growth and on cell integrity signalling using such reporter strains. Tea tree oil was found to inhibit growth of wild-type and slg1/wsc1 mutant cells at a threshold of approximately 0.1% v/v, with the purified compounds acting already at half these concentrations. A mid2 deletion displayed hyper-resistance. Tea tree oil also induces the signalling pathway in a dose-dependent manner.

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“…Cerulenin, an antibiotic produced by the fungus Cephalosporium caerulens (41), is known to specifically inhibit a number of [~-ketoacyl-thioester synthases (8,67) by an irreversible mechanism (8). Therefore, [3H]-cerulenin was used to tag such enzymes in crude protein extracts of E. coli before purification.…”

Section: Purification Of P-ketoacyi-acp Synthase Imentioning

confidence: 99%

β-ketoacyl-ACP synthase I of Escherichia coli: Nucleotide sequence of thefabB gene and identification of the cerulenin binding residue

Kauppinen

Siggaard-Andersen

1988

Carlsberg Res. Commun.

159

124

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Cephalosporium caerulens, polyketideThe fabB gene of E. coli encoding ~-ketoacyl-ACP synthase I has been isolated by complementation and sequenced. The enzyme has been purified and its NH2-terminal residues sequenced. Identification of the active site was accomplished by tagging with 3H-cerulenin and radio sequencing of the region. Comparison of the deduced primary structures of thefabB gene product with the FAS2 gene product of Saccharomyces cerevisiae revealed the probable active site in chalcone synthases of higher plants.

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Inhibition of fatty acid synthetases by the antibiotic cerulenin

Cited by 267 publications

References 7 publications

Production of valuable compounds by molds and yeasts

Production of valuable compounds by molds and yeasts

The effect of tea tree oil and antifungal agents on a reporter for yeast cell integrity signalling

β-ketoacyl-ACP synthase I of Escherichia coli: Nucleotide sequence of thefabB gene and identification of the cerulenin binding residue

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