Dynamics of l-valine in relation to the production of cyclosporin A by Tolypocladium inflatum

1991 ◽  
Vol 34 (4) ◽  
Author(s):  
J. Lee ◽  
S.N. Agathos
Keyword(s):  
Cyclosporin A ◽  
Tolypocladium Inflatum

Biosynthesis of cyclosporin A: partial purification and properties of a multifunctional enzyme from Tolypocladium inflatum

Biochemistry ◽  
1986 ◽  
Vol 25 (3) ◽  
pp. 550-553 ◽  
Author(s):  
Rainer Zocher ◽  
Takuya Nihira ◽  
Edith Paul ◽  
Norbert Madry ◽  
Hugo Peeters ◽  
...  
Keyword(s):  
Cyclosporin A ◽  
Partial Purification ◽  
Tolypocladium Inflatum ◽  
Multifunctional Enzyme ◽  
Purification And Properties

Cyclosporin-A production by Tolypocladium inflatum using solid state fermentation

1999 ◽  
Vol 34 (3) ◽  
pp. 269-280 ◽  
Author(s):  
M.V. Ramana Murthy ◽  
E.V.S. Mohan ◽  
A.K. Sadhukhan
Keyword(s):  
Solid State ◽  
Cyclosporin A ◽  
Solid State Fermentation ◽  
Tolypocladium Inflatum

Production of cyclosporin a by carrageenan-immobilized tolypocladium inflatum in an airlift reactor with external loop

1983 ◽  
Vol 5 (10) ◽  
pp. 693-696 ◽  
Author(s):  
B. C. Foster ◽  
R. T. Coutts ◽  
F. M. Pasutto ◽  
J. B. Dossetor
Keyword(s):  
Cyclosporin A ◽  
Airlift Reactor ◽  
Tolypocladium Inflatum ◽  
External Loop

scholarly journals Cyclosporine A nephropathy, its pathogenesis and management

KIDNEYS ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 186-189
Author(s):  
Yusuf Erçin Sonmez
Keyword(s):  
Cyclosporin A ◽  
Tissue Oxygenation ◽  
Morphological Changes ◽  
Early Period ◽  
Late Toxicity ◽  
Great Success ◽  
Tolypocladium Inflatum ◽  
Rat Models ◽  
Underlying Factor ◽  
Early Toxicity

CsA, obtained from a fungus called Tolypocladium inflatum came into medical use in 1983. Organ transplants have shown great success after the use of Cyclosporine, especially in 3- and 5-year graft survival. However, nephrotoxicity seen in the early and late periods complicates its use. It is very important to distinguish especially early toxicity from rejection attacks; because the treatments of both processes are completely different. While vasocostriction in the renal artery system is prominent in the early period, the underlying factor for late toxicity is the thickening of the arteriolar intima and the consequent decrease in tissue oxygenation. The article discusses the variants of toxicity caused by the use of cyclosporin A. Morphological changes with the use of cyclosporin A are shown in rat models. The results of our own observations on the use of prostaglandin, which demonstrated the effect of vasodilation, are also presented, which can probably be used for further studies in order to reduce the nephrotoxicity of cyclosporin A. In particular, we found that PGE2 significantly reduced vasoconstriction and reduced the toxic effect due to CsA. The limitations was the usage of these agents once, so we couldn’t continue and only gave them intravenously. However, the results obtained were found to be significant.

scholarly journals Cyclosporine Biosynthesis in Tolypocladium inflatum Benefits Fungal Adaptation to the Environment

mBio ◽  
2018 ◽  
Vol 9 (5) ◽  
Author(s):  
Xiuqing Yang ◽  
Peng Feng ◽  
Ying Yin ◽  
Kathryn Bushley ◽  
Joseph W. Spatafora ◽  
...  
Keyword(s):  
Amino Acid ◽  
Antifungal Activity ◽  
Cyclosporin A ◽  
Gene Cluster ◽  
Pathogenic Fungus ◽  
Alanine Racemase ◽  
Tolypocladium Inflatum ◽  
Fungal Virulence ◽  
Immunosuppressant Drug ◽  
Genes Encoding

ABSTRACT The cycloundecapeptide cyclosporin A (CsA) was first isolated from the insect-pathogenic fungus Tolypocladium inflatum for its antifungal activity and later developed as an immunosuppressant drug. However, the full biosynthetic mechanism of CsA remains unknown and has puzzled researchers for decades. In this study, the biosynthetic gene cluster is suggested to include 12 genes encoding enzymes, including the nonribosomal peptide synthetase (NRPS) (SimA) responsible for assembling the 11 amino acid substrates of cyclosporine and a polyketide synthase (PKS) (SimG) to mediate the production of the unusual amino acid (4R)-4-[(E)-2-butenyl]-4-methyl-l-threonine (Bmt). Individual deletion of 10 genes, isolation of intermediates, and substrate feeding experiments show that Bmt is biosynthesized by three enzymes, including SimG, SimI, and SimJ. The substrate d-alanine is catalyzed from l-alanine by alanine racemase SimB. Gene cluster transcription is regulated by a putative basic leucine zipper (bZIP)-type protein encoded by the cluster gene SimL. We also found that the cluster cyclophilin (SimC) and transporter (SimD) genes contribute to the tolerance of CsA in the CsA-producing fungus. We also found that cyclosporine production could enable the fungus to outcompete other fungi during cocultivation tests. Deletion of the CsA biosynthetic genes also impaired fungal virulence against insect hosts. Taking all the data together, in addition to proposing a biosynthetic pathway of cyclosporines, the results of this study suggest that CsA produced by this fungus might play important ecological roles in fungal environment interactions. IMPORTANCE The cyclopeptide cyclosporin A was first isolated from the filamentous fungus Tolypocladium inflatum showing antifungal activity and was later developed as an immunosuppressant drug. We report the biosynthetic mechanism of cyclosporines that are mediated by a cluster of genes encoding NRPS and PKS controlled by a bZIP-type transcriptional regulator. The two unusual amino acids Bmt and d-Ala are produced by the PKS pathway and alanine racemase, respectively. The cyclophilin and transporter genes jointly contribute to fungal self-protection against cyclosporines. Cyclosporine confers on T. inflatum the abilities to outcompete other fungi in competitive interactions and to facilitate fungal infection of insect hosts, which therefore benefits fungal adaptations to different environments.

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