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Role of some fermentation parameters on cyclosporin A production by a new isolate of Aspergillus terreus. Presented by

Role of some fermentation parameters on cyclosporin A production by a new isolate of Aspergillus terreus. Presented by SEEMA RENU. Struture of Cyclosporin A. Cyclosporin A is a cyclopeptide composed of 11 amino acids

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Role of some fermentation parameters on cyclosporin A production by a new isolate of Aspergillus terreus. Presented by

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  1. Role of some fermentation parameters on cyclosporin A production by a new isolate of Aspergillus terreus.Presented bySEEMA RENU

  2. Struture of Cyclosporin A • Cyclosporin A is a cyclopeptide composed of 11 amino acids • It was first derived from submerged culture of aerobic fungi identified as strains of Trichoderma polysporum. • Trichoderma polysporum currently identified as Tolypocladium inflatum also known as Tolypocladium niveum. • T. inflatum also produces numerous other cyclosporins all composed of 11 amino acids differing from one another in only one amino acid. • For example the second amino acid in cyclosporine A is alpha amino butyric acid whereas that in cyclosporine B is alanine.

  3. Discovery of Cyclosporin A • It was discovered in the early 1970 by research workers at Sandoz, Ltd in Basel, Switzerland during a search for fungal metabolites with antibiotic properties. • One of the metabolites released, known as 24-556 had antifungal properties and very low toxicity toward the mammalian cells when tested at Sandoz. • The two components of 24-556 were termed as Cyclosporin A and Cyclosporin B where as Cycloporin A was much more active than Cyclosporine B. • Human transplantation was first performed in 1978 using cyclosporin A. Since then it has a major role in allogenic transplantation and autoimmune diseases.

  4. Mechanism of action • Cyclosporin A works by selectively affecting the production of T and B lymphocytes produced in the bone marrow and thymus. • Individuals with autoimmune diseases such as rheumatoid arthritis produces excessive amount of toxic molecules such as reactive oxygen intermediates that cause inflammation in the joints. • Cy A reduces the inflammation by selectively acting against the production of these lymphocytes.

  5. A macrophage engulfing a bacterium and releasing packets of toxic molecules (reactive oxygen intermediates) that breaks down and destroy the bacterium

  6. Cyclosporin A and kidney damage • The widespread use of cyclosporin A showed that it causes damage to the kidneys. • Studies proved that the damage can be avoided by using cyclosporin A in lower amounts and in conjunction with a steroid called prednisone.

  7. Fermentation parameters and Cy A production by A. Terreus • The conditions affecting the production of Cy A by A. Terreus included the composition of the cultivation medium, fermentation time course, inoculum nature, medium volume, agitation rate and pH value. • Different fungi were investigated for Cy A production. • – sign indicated no production of Cy A, ++ showed a moderate amount of Cy A production, whereas three +++ means higher production of Cy A as judged by the darkness of the colony color.

  8. The yield of the Cy A increased as the fermentation time course increased. The highest yield of Cy A in mg/ml was on the day 10. The biomass yield of A. terreus (g/l) was kept on decreasing after day 10.

  9. The best yield of Cy A was obtained by a 48-h-old culture. As the age increased production of Cy A start to decrease.

  10. Maximum yield of Cy A was obtained when the volume of the inoculum size was 2ml/100ml.

  11. The size of the medium also affected the production of Cy A. A 250 ml Erlenmeyer flask containing production medium equal to 100ml afforded the highest production of Cy A

  12. The formation of Cy A by A.terreus was also affected by the agitation rate. The maximum production was at 200 rpm

  13. The production was maximum in an acidic medium with a pH 5.3. Cy A production decreased with an increase in pH.

  14. Buffer is a partially neutralised acid that resists changes in pH. The results showed that on using citrate buffer the maximum yield (84.22 mg/L) of Cy A was obtained. Increased pH also affected the texture of the fungal pellets by making it weaker.

  15. RESULTS • The considerable amount of Cy A as a secondary metabolite, was produced under above described conditions, proved A. terreus as a potential source. • Still no data on its use for Cy A production. • It does used to extract lovastatin an agent used to lower cholesterol.

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