Influence of amino acids on the biosynthesis of cyclosporin A by Tolypocladium inflatum

1996 ◽  
Vol 45 (6) ◽  
pp. 800-803 ◽  
Author(s):  
K. Balakrishnan ◽  
A. Pandey
Keyword(s):  
Amino Acids ◽  
Cyclosporin A ◽  
Tolypocladium Inflatum

The immunosuppressant FK506 inhibits amino acid import in Saccharomyces cerevisiae

1993 ◽  
Vol 13 (8) ◽  
pp. 5010-5019 ◽  
Author(s):  
J Heitman ◽  
A Koller ◽  
J Kunz ◽  
R Henriquez ◽  
A Schmidt ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Amino Acids ◽  
Amino Acid ◽  
Cyclosporin A ◽  
Secretory Pathway ◽  
Yeast Cells ◽  
Amino Acid Transporters ◽  
Yeast Saccharomyces Cerevisiae ◽  
Eukaryotic Microorganisms

The immunosuppressants cyclosporin A, FK506, and rapamycin inhibit growth of unicellular eukaryotic microorganisms and also block activation of T lymphocytes from multicellular eukaryotes. In vitro, these compounds bind and inhibit two different types of peptidyl-prolyl cis-trans isomerases. Cyclosporin A binds cyclophilins, whereas FK506 and rapamycin bind FK506-binding proteins (FKBPs). Cyclophilins and FKBPs are ubiquitous, abundant, and targeted to multiple cellular compartments, and they may fold proteins in vivo. Previously, a 12-kDa cytoplasmic FKBP was shown to be only one of at least two FK506-sensitive targets in the yeast Saccharomyces cerevisiae. We find that a second FK506-sensitive target is required for amino acid import. Amino acid-auxotrophic yeast strains (trp1 his4 leu2) are FK506 sensitive, whereas prototrophic strains (TRP1 his4 leu2, trp1 HIS4 leu2, and trp1 his4 LEU2) are FK506 resistant. Amino acids added exogenously to the growth medium mitigate FK506 toxicity. FK506 induces GCN4 expression, which is normally induced by amino acid starvation. FK506 inhibits transport of tryptophan, histidine, and leucine into yeast cells. Lastly, several genes encoding proteins involved in amino acid import or biosynthesis confer FK506 resistance. These findings demonstrate that FK506 inhibits amino acid import in yeast cells, most likely by inhibiting amino acid transporters. Amino acid transporters are integral membrane proteins which import extracellular amino acids and constitute a protein family sharing 30 to 35% identity, including eight invariant prolines. Thus, the second FK506-sensitive target in yeast cells may be a proline isomerase that plays a role in folding amino acid transporters during transit through the secretory pathway.

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

scholarly journals The immunosuppressant FK506 inhibits amino acid import in Saccharomyces cerevisiae.

1993 ◽  
Vol 13 (8) ◽  
pp. 5010-5019 ◽  
Author(s):  
J Heitman ◽  
A Koller ◽  
J Kunz ◽  
R Henriquez ◽  
A Schmidt ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Amino Acids ◽  
Amino Acid ◽  
Cyclosporin A ◽  
Secretory Pathway ◽  
Yeast Cells ◽  
Amino Acid Transporters ◽  
Yeast Saccharomyces Cerevisiae ◽  
Eukaryotic Microorganisms

The immunosuppressants cyclosporin A, FK506, and rapamycin inhibit growth of unicellular eukaryotic microorganisms and also block activation of T lymphocytes from multicellular eukaryotes. In vitro, these compounds bind and inhibit two different types of peptidyl-prolyl cis-trans isomerases. Cyclosporin A binds cyclophilins, whereas FK506 and rapamycin bind FK506-binding proteins (FKBPs). Cyclophilins and FKBPs are ubiquitous, abundant, and targeted to multiple cellular compartments, and they may fold proteins in vivo. Previously, a 12-kDa cytoplasmic FKBP was shown to be only one of at least two FK506-sensitive targets in the yeast Saccharomyces cerevisiae. We find that a second FK506-sensitive target is required for amino acid import. Amino acid-auxotrophic yeast strains (trp1 his4 leu2) are FK506 sensitive, whereas prototrophic strains (TRP1 his4 leu2, trp1 HIS4 leu2, and trp1 his4 LEU2) are FK506 resistant. Amino acids added exogenously to the growth medium mitigate FK506 toxicity. FK506 induces GCN4 expression, which is normally induced by amino acid starvation. FK506 inhibits transport of tryptophan, histidine, and leucine into yeast cells. Lastly, several genes encoding proteins involved in amino acid import or biosynthesis confer FK506 resistance. These findings demonstrate that FK506 inhibits amino acid import in yeast cells, most likely by inhibiting amino acid transporters. Amino acid transporters are integral membrane proteins which import extracellular amino acids and constitute a protein family sharing 30 to 35% identity, including eight invariant prolines. Thus, the second FK506-sensitive target in yeast cells may be a proline isomerase that plays a role in folding amino acid transporters during transit through the secretory pathway.

Renal Effects of Amino Acids and Dopamine in Renal Transplant Recipients Treated with or without Cyclosporin A

1996 ◽  
Vol 91 (4) ◽  
pp. 489-496 ◽  
Author(s):  
Jesper Melchior Hansen ◽  
Niels Vidiendal Olsen ◽  
Paul Peter Leyssac
Keyword(s):  
Amino Acids ◽  
Glomerular Filtration Rate ◽  
Renal Transplant ◽  
Cyclosporin A ◽  
Glomerular Filtration ◽  
Plasma Flow ◽  
Filtration Rate ◽  
Renal Plasma Flow ◽  
Renal Transplant Recipients ◽  
Transplant Recipients

1. The nephrotoxic effects of cyclosporin A may diminish the ability of the transplanted kidney to increase the glomerular filtration rate and effective renal plasma flow during infusion of dopamine or amino acids. 2. The present study included 16 renal transplant recipients transplanted for more than 6 months. Eight of the patients were on immunosuppressive treatment including cyclosporin A [cyclosporin A group; cyclosporin A dose, 2.7 ± 0.4 mg/kg; S-creatinine, 105 ± 12 μmol/l (means ± SEM)], whereas eight patients had never received cyclosporin A (non-cyclosporin A group; S-creatinine, 89 ± 6 μmol/l). The renal response to infusion of dopamine and of amino acids was investigated on two separate days. All clearance measurements were carried out at nadir cyclosporin A blood levels. 3. Effective renal plasma flow increased significantly in the non-cyclosporin A group and cyclosporin A group by 31.0 ± 4.1% and 35.9 ± 6.6%, respectively, during infusion of dopamine, and by 18.7 ± 6.7% and 13.9 ± 5.3%, respectively, during infusion of amino acids. Glomerular filtration rate increased significantly in the non-cyclosporin A group and cyclosporin A group by 15.7 ± 3.3% and 18.3 ± 4.7%, respectively, during infusion of dopamine, and by 18.9 ± 4.5% and 15.0 ± 3.7%, respectively, during infusion of amino acids. 4. Furthermore, the amino acid- and dopamine-induced increases in proximal tubular outflow (renal clearance of lithium) and calculated changes in renal proximal and distal tubular handling of sodium (and water) were comparable between the two groups of patients. Dopamine caused significant natriuresis in both groups. 5. In conclusion, low-dose cyclosporin A seems not to attenuate the renal haemodynamic and tubular response to infusions of amino acids and of dopamine in renal transplant recipients with a good graft function.

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
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