Process for manufacturing cyclosporin a by highly productive fusant strain

Abstract

The present invention relates to a process for making a highly productive fusant of Tolypocladium inflatum, a producing strain of cyclosporin A with immunosuppressive properties wherein the selection of the fusant KD461, designed to produce a large amount of cyclosporin A, was made available by the following steps of: developing amino acid-dependent mutants of Tolypocladium inflatum, wild strain isolated from soil, which mutants are induced by UV radiation; conjugating L-valine-dependent and L-leucine-dependent mutants to promote the demand and utility of L-valine and L-leucine, precursors of cyclosporin A, together with an organic nitrogen-source. The fusant KD461 produced has the following characteristics in comparison with wild strain: 1) it is slow growing in a solid malt-yeast extract agar medium, b) the surface of the colony is light grey in color and is therefore darker than the mild strain, c) the backside of the colony is dark brown, and d) in a liquid medium it has short and thick hyphae with many arthrospore.

Dependencies are inferred from the claim text.