The Fungal Production of Cyclosporine<sup>a</sup>

Agathos, Spiros N.; Madhosingh, C.; Marshall, J. W.; Lee, J.

doi:10.1111/j.1749-6632.1987.tb23863.x

Cited by 30 publications

(12 citation statements)

References 10 publications

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“…1,188.6) showed a molecular weight of 1,189, while that of cyclosporin C (Mw, 1,218.6) was 1,219, both samples corresponding to the published structures (1) and their expected elution sequence from a reverse-phase HPLC column on the basis of their hydrophobicity. All three isolated cyclosporins inhibited the growth and sporulation of A. niger on agar plates.…”

Section: Methodsmentioning

confidence: 99%

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Production of cyclosporins by Tolypocladium niveum strains

Isaac

Jones

Pickard

1990

Antimicrob Agents Chemother

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Nine strains of Tolypocladium niveum (=inflatum) were compared for their production of cyclosporins. Two of the strains, which were originally from the parental NRRL 8044 strain, were among the lower producers, while seventeen Tolypocladium strains belonging to seven other species produced no detectable cyclosporins. Variable cyclosporin production was observed initially. Once extraction and quantitation methods had been established, spore inoculum density and cultural morphology and carbon and nitrogen sources were found to be among the variables affecting cyclosporin production. Cyclosporin A was identified by cochromatography by using high-performance liquid chromatography, and cyclosporins A, B, and C were identified by gas chromatography-mass spectroscopy; all three compounds exhibited biological activity. They were routinely produced as a mixture in the ratio 7:1:2 in T. niveum UAMH 2472, which was selected on the basis of single-spore isolate total cyclosporin production and was used for most studies. This strain routinely produced total cyclosporin levels of 150 to 200 mg. liter-' after 12 days of growth on a 2% sorbose-1% vitamin assay Casamino Acids medium.

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Section: Methodsmentioning

confidence: 99%

“…inflatum ATCC 34921 but that maltose was preferred by their mutant M6 strain (1). Recently, directed synthesis of cyclosporins by using valine and leucine has been shown in a glucose-adapted wild-type strain (16), and this group also described cyclosporin production by the fungus immobilized in porous celite beads (7).…”

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confidence: 96%

Production of cyclosporins by Tolypocladium niveum strains

Isaac

Jones

Pickard

1990

Antimicrob Agents Chemother

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“…As mentioned, of all the closely related Beauveria and Tolypocladium strains, the CPA element is present in multiple copies only in the ATCC34921 strain, which is known as a cyclosporin producer [25]. It seems likely that a RecQ helicase-like gene was present in the common ancestor of Tolypocladium and Beauveria strains since single copies of it have been previously detected [14].…”

Section: Resultsmentioning

confidence: 95%

The Tolypocladium inflatum CPA element encodes a RecQ helicase‐like gene

Kempken

2008

J. Basic Microbiol.

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Previously, a repetitive CPA element was discovered in the genome of the filamentous fungus Tolypocladium inflatum; however, no further characterization was technically possible at that time. In this study, PCR amplification was used to detect a 4 kb conserved portion of the CPA element that appeared to be present in most, if not all, genomic CPA elements. The amplicons included a large open reading frame that was most similar to a RecQ helicase-like gene from Metarhizium anisopliae. The repetitive nature of the CPA element suggests that it is related to the eukaryotic Helitron class of transposable elements.

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“…Of the complex nitrogen sources, casamino acids produced the most constant data and the cleanest extract. The favourable carbon sources for many strains of T inflaturn were described by AGATHOS et al [254] ad ZHAO et al [258]. The various steps involved in the isolation and purification of cyclosporin from the fermented samples is given in Fig.…”

Section: Microbiology Of Cyclosporin Productionmentioning

confidence: 98%

The panorama of cyclosporin research

Balakrishnan

Pandey

1996

J. Basic Microbiol.

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Cyclosporin, a novel drug, exhibiting unique discriminatory action on the activation of helper lymphocytes without the undesirable side effects associated with conventional immunosuppressants, can well be considered as the prototype of a new generation of immunosuppressants. It is probably the first one to demonstrate that an immunopharmacologic approach to the modulation of the immune response by drugs is feasible. This enabled a decisive step forward to be made in transplantation surgery, particularly in the field of heart and kindney transplantation.Cyclosporin A exerts antifungal, antiparasitic and antiinflammatory activities also. There is considerable interest in the prospective value of this drug in the treatment of autoimmune disorders. Accolades are to be given for its role as a tool for studying mechanisms of the immune system. This review is an attempt to look into the various strides it had evolved before attaining the status of a unique drug, and also to assess critically the prospective value of this potent drug.The present modem era of antibiotic research is characterized by advanced screening procedures aiming specifically not only at antibacterials or antifungals but at compounds like enzyme inhibitors, immunomodulators and antitumor drugs. New sources of rare microorganisms are currently under exploitation. Development of microbial products with new medicinal activties has turned out to be a big research area, spearheaded by the success story of small molecular weight immunomodulators. Long accepted as the best way to prevent or treat rejection in patients undergoing organ transplantation, immunosuppressive therapy is attracting increased attention for its ability to treat a variety of diseases. One such potent agent, widely acclaimed as the first of a new generation of remarkable immunosuppressive agents, cyclospofin is being used in novel ways in a wide array of conditions.The cyclosporins are a group of over 25 closely related cyclic undecapeptides produced as secondary metabolites by two strains of fungi imperfecti, Cylindrocarpum lucidum BOOTH and Tolypocladium inflaturn CAMS, isolated from soil samples. Cyclosporin A is the main component of this family of cyclic peptides each containing 11 amino acids.This review is a survey of the works of a large team of chemists, biologists, clinicians, toxicologists and pharmacologists which lead to the development of a new drug of choice and the impact that this drug in particular is having and hopefully other similar ones will have in the field of immunopharmacology. Discovery of cyclosporinThe cyclosporins were originally discovered in 1970 by scientists at Sandoz Laboratory in Switzerland while attempting to identify new antifungal agents [ 11. Crude extracts of two new 9 J. Basic Microbiol. 36 (1996) 2 122 K. BALAKRISHNAN AND A. PANDEY strains of fungi imperfecti Cylindrocarpon lucidium, BOOTH and Tolypocladium inflaturn CAMS demonstrated a narrow spectrum of activity in vitro mainly against clinically irrelevant organisms. However, the antifunga...

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The Fungal Production of Cyclosporine^a

Cited by 30 publications

References 10 publications

Production of cyclosporins by Tolypocladium niveum strains

Production of cyclosporins by Tolypocladium niveum strains

The Tolypocladium inflatum CPA element encodes a RecQ helicase‐like gene

The panorama of cyclosporin research

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The Fungal Production of Cyclosporinea

Cited by 30 publications

References 10 publications

Production of cyclosporins by Tolypocladium niveum strains

Production of cyclosporins by Tolypocladium niveum strains

The Tolypocladium inflatum CPA element encodes a RecQ helicase‐like gene

The panorama of cyclosporin research

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The Fungal Production of Cyclosporine^a