The formation of butenyl-methyl-L-threonine is performed by a Bmt polyketide synthase that uses acetate/malonate as its starting material. Gene cluster
Tolypocladium inflatum, the species currently used for mass production of Cyclosporin, has the biosynthetic genes arranged into a 12-gene cluster. Of these 12 genes, SimA (Q09164) is the cyclosporin synthetase, SimB (CAA02484.1) is the alanine racemase, and SimG (similar to ATQ39432.1) is the polyketide synthase. These genes are associated with an active retrotransposon. Although these sequences are poorly-annotated on GenBank and other databases, 90% similar sequences can be found for the Cyclosporin-producing Beauveria felina (or Amphichorda ~). SimB has two paralogs in the same organism with different but overlapping functions thanks to their low speficity. History
In 1970, new strains of fungi were isolated from soil samples taken from Norway and from Wisconsin in the US by employees of Sandoz (now Novartis) in Basel, Switzerland. Both strains produced a family of natural products called cyclosporins. Two related components that had antifungal activity were isolated from extracts from these fungi. The Norwegian strain, Tolypocladium inflatum Gams, was later used for the large scale fermentation of ciclosporin.The immunosuppressive effect of the natural product ciclosporin was discovered on January 31, 1972 in a screening test on immune suppression designed and implemented by Hartmann F. Stähelin at Sandoz. The chemical structure of cyclosporin was determined in 1976, also at Sandoz. The success of the drug candidate ciclosporin in preventing organ rejection was shown in kidney transplants by R.Y.
These symptoms have been related to Sick Building Syndrome, which involves symptoms such as irritation to the eyes, skin, and upper airways, headache and fatigue.The eye is also a source of chronic irritation. Disorders like Sjögrens syndrome, where one does not make tears, can cause a dry eye sensation which feels very unpleasant. The condition is difficult to treat and is lifelong. Besides artificial tears, there is a drug called Restasis which may help.Blepharitis is dryness and itching on the upper eyelids. This condition is often seen in young people and can lead to reddish dry eye and scaly eyebrows. To relieve the itching sensation, one may need to apply warm compresses and use topical corticosteroid creams. Skin
Eczema is another cause of chronic irritation and affects millions of individuals. Eczema simply means a dry skin which is itchy. The condition usually starts at an early age and continues throughout life. The major complaint of people with eczema is an itchy dry skin. Sometimes, the itching will be associated with a skin rash. The affected areas are always dry, scaly, reddish and may ooze sometimes. Eczema cannot be cured, but its symptoms can be controlled. One should use moisturizers, use cold compresses and avoid frequent hot showers. There are over the counter corticosteroids creams which can be applied. Sometimes, an anti histamine has to be used to prevent the chronic itching sensations. There are also many individuals who have allergies to a whole host of substances like nuts, hair, dander, plants and fabrics.