Production of ergotamine by a strain ofClaviceps purpurea (Fr.) Tul.

Amici, Alba M.; Minghetti, A.; Scotti, T.; Spalla, C.; Tognoli, L.

doi:10.1007/bf01901174

Cited by 41 publications

(22 citation statements)

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“…[13] In fact, cytochrome P450-related oxygenase activities that catalyze the conversion of agroclavine to elymoclavine were detected in the particulate fractions of both clavine-producing C. fusiformis SD58 and ergopeptine producing C. purpurea PCCE1, [12,13] which like our C. purpurea P1 [16] is derived from the same ancestor, C. purpurea FI 32/17. [26] Interestingly enough, the microsomal fraction of strain PCCE1 harbored an additional activity that catalyzed the conversion of elymoclavine to paspalic acid which was absent in clavineproducing C. fusiformis SD58. [13] It was not shown, however, whether the agroclavine monooxygenases from the two strains were identical.…”

Section: Discussionmentioning

confidence: 99%

Identification of the Cytochrome P450 Monooxygenase that Bridges the Clavine and Ergoline Alkaloid Pathways

et al. 2006

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Clavines and D-lysergic acid-derived alkaloid amides and alkaloid peptides are two different families of compounds that have the indole-derived tetracyclic metergoline ring system in common. Previous work has shown that D-lysergic acid is biosynthetically derived from clavine alkaloids. Recent cloning and analysis of the ergot alkaloid biosynthesis gene cluster from the D-lysergic acid peptide (ergopeptines)-producing Claviceps purpurea, has shown that it most probably contains all genes necessary for D-lysergic acid synthesis as well as those that encode the assembly of D-lysergic acid peptides, such as ergotamine. To address the role of the oxygenase genes of alkaloid-gene clusters, the only cytochrome P450 monooxygenase gene of this cluster was inactivated by disruption. The resultant mutant accumulated agroclavine, elymoclavine, and chanoclavine in substantial amounts but not ergopeptines. Feeding the mutant with D-lysergic acid restored ergopeptine synthesis; this suggests a block in the conversion of elymoclavine to D-lysergic acid. The gene was designated cloA (for encoding a clavine oxidase, CLOA). Retransformation of the mutant with the intact cloA gene also restored ergopeptine synthesis. These data show that CLOA catalyses the conversion of clavines to D-lysergic acid, it acts as a critical enzyme in the ergot alkaloid gene cluster, and bridges the biosynthesis of the two different families of alkaloids.

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Section: Discussionmentioning

confidence: 99%

Identification of the Cytochrome P450 Monooxygenase that Bridges the Clavine and Ergoline Alkaloid Pathways

et al. 2006

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“…Strain Ecc93 was cultivated according to Kobel and Sanglier (13). Inoculum medium and medium T25 were used for alkaloid fermentations (14,15). In some occasions a modified Vogel's medium was used (12,16 [9,10-3 H]-9,10-Dihydrolysergic acid was prepared from [9,10-3 H]-9,10-dihydroergocryptine as described previously (9).…”

Section: Methodsmentioning

confidence: 99%

“…For enzyme extraction from strain D1, cells were harvested after 70 h of growth in inoculum medium or 120 h of growth in T25 medium. At these times the cultures were starting the main ergotamine accumulation phase (15). Ergotamine was already detectable at ϳ10 mg/liter after 36 h of growth in T25 medium.…”

Section: Purification Of D-lysergylmentioning

confidence: 98%

“…Fig. 4 14 C-labeled compounds to the fluorophor used in these experiments, the faint labeling may be due to the high K m values for alanine and proline (see below) and the fact that purified enzyme preparations usually contain varying amounts of amino acids already bound to the enzyme. This can also explain uneven product labeling (9).…”

Section: Purification Of D-lysergylmentioning

confidence: 99%

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D-Lysergyl Peptide Synthetase from the Ergot Fungus Claviceps purpurea

Riederer

Han

Keller

1996

Journal of Biological Chemistry

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“…Chain, the Nobel Prize Laureate for Medicine in 1945 for his studies of penicillin structure and production. Microbiological and chemical studies in the ISS and FI laboratories realized a methodology for producing lysergic acid, ergotamine, and derivatives in submerged cultures of fungal strains of Claviceps paspalis and Claviceps purpurea (2,3). Another Nobel Prize Laureate for Medicine, Prof. D. Bovet, awarded in 1957 for his studies concerning the mechanism of action of sulfamides, antihistaminics, and synthetic curares, directed the ISS laboratories of Therapeutic Chemistry in Rome from 1947 to 1964.…”

Section: Introductionmentioning

confidence: 99%

The Roots of Modern Oncology: From Discovery of New Antitumor Anthracyclines to their Clinical Use

Cassinelli

2016

Tumori

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In May 1960, the Farmitalia CEO Dr. Bertini and the director of the Istituto Nazionale dei Tumori of Milan Prof. Bucalossi (talent scout and city's Mayor) signed a research agreement for the discovery and development up to clinical trials of new natural antitumor agents. This agreement can be considered as a pioneering and fruitful example of a translational discovery program with relevant transatlantic connections. Owing to an eclectic Streptomyces, found near Castel del Monte (Apulia), and to the skilled and motivated participants of both institutions, a new natural antitumor drug, daunomycin, was ready for clinical trials within 3 years. Patent interference by the Farmitalia French partner was overcome by the good quality of the Italian drug and by the cooperation between Prof. Di Marco, director of the Istituto Ricerche Farmitalia Research Laboratories for Microbiology and Chemotherapy, and Prof. Karnofsky, head of the Sloan-Kettering Cancer Institute of New York, leading to the first transatlantic clinical trials. The search for daunomycin's sister anthracyclines led to the discovery and development of adriamycin, one of the best drugs born in Milan. This was the second act prologue of the history of Italian antitumor discovery and clinical oncology, which started in July 1969 when Prof. Di Marco sent Prof. Bonadonna the first vials of adriamycin (doxorubicin) to be tested in clinical trials. This article reviews the Milan scene in the 1960s, a city admired and noted for the outstanding scientific achievements of its private and public institutions in drugs and industrial product discovery.

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Production of ergotamine by a strain ofClaviceps purpurea (Fr.) Tul.

Cited by 41 publications

References 0 publications

Identification of the Cytochrome P450 Monooxygenase that Bridges the Clavine and Ergoline Alkaloid Pathways

Identification of the Cytochrome P450 Monooxygenase that Bridges the Clavine and Ergoline Alkaloid Pathways

D-Lysergyl Peptide Synthetase from the Ergot Fungus Claviceps purpurea

The Roots of Modern Oncology: From Discovery of New Antitumor Anthracyclines to their Clinical Use

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