The main objective of the project is to produce the immunosuppressant drug, Cyclosporine from Tolypocladium Inflatum. Patients who undergo solid organ transplantation require an immunosuppressive drug to prevent rejection by decreasing the body's own natural defense to foreign tissues, and Cyclosporin A is one of the most commonly used immunosuppressive drugs in the organ transplantations.
Cyclosporin A is a cyclic nonribosomal peptide, consisting of 11 amino acids and synthesized through an enzyme called Cyclosporin synthetase (CySyn). This enzyme is found in a few other fungal species and Cyclosporine are produced as secondary metabolites by strains of fungi. The most commonly used fungi class is T. inflatum, …show more content…
Numerous applications has been identified so far, and this will result in a growing global commercial demand for Cyclosporine A. According to IMS Health, In 2010 the immunosuppression market for transplant patients in the US, Japan, UK, France, Germany, Italy, and Spain totaled $5.0 billion and of that $870 million was only for Cyclosporine A. That would make the Cyclosporin 0.174 of the immunosuppression market.
Cyclosporin A is an expensive drug. The average yearly costs of the drug for a patient is approximately $8200 [1] This demand led researchers to improve the production and yield, to reduce the cost of the product. Cyclosporin A is a maintenance drug, which means that it has to be used long-term by transplant patients.[2] When considering the cost of the drug for one person, one would get that there are approximately 106098 patients that use the Cyclosporin A regularly over a period of a year. The dose of the drug varies over time. In the first six months, a dosage of 2.5 mg/kg is used. In the next 6 months a dosage of 0.15 mg/kg is used [3]. This would make the average usage of a patient in a day 1.325 mg/kg and 483.625 mg/kg in a year. Since there are 106098 patients who use this drug yearly, their usage would be 51,311,645 mg/kg. If the average weight of humans were to be taken as 75 kg, then 3,848,373 kg/year for all …show more content…
The species are characterized by white slow growing cottony colonies that belong to the family of conidiophore generating Ascomycota. The conidiophores are usually short and bear lateral or terminal whorls of phialides which have a swollen, sometimes cylindrical base and thin, often bent necks. The conidia are one celled, hyaline, and formed in slimy heads [4].
T.inflatum
T.inflatum, also known as Trichoderma polysporum and Beauveria nivea. The Tolypocladium genus was first described by Gams in 1971 as a new genus of soil Moniliales. Its characteristic properties are slow growth, pillow-like white colonies, terminal and lateral phialides developed partly on a short side-branch, with strongly swollen base and filamentous [5].
Tolypocladium inflatum is used as the microorganism which is the best one suited to produce Cyclosporin A as high amounts of the drug can be produced with it.
The ideal moisture for T. inflatum was determined as 60% - 70%, the optimum pH as 2,and an incubation temperature of 25°C.
F.solani
The pH of F.solani was determined to be 2.0 to 9.0. These, optimum values were retrieved from different studies.
Fusarium