公开(公告)号：US5856141A

公开(公告)日：1999-01-05

申请号：US817392

申请日：1997-04-18

申请人： Jung Woo Kim ,  Kwang Moo Lee ,  Byoung Tack Choi ,  Jin Man Lee ,  Nak Kyu Sung ,  Kyeong Bok Min

发明人： Jung Woo Kim ,  Kwang Moo Lee ,  Byoung Tack Choi ,  Jin Man Lee ,  Nak Kyu Sung ,  Kyeong Bok Min

IPC分类号： C07K7/64 ,  C12N1/14 ,  C12P21/04 ,  C12R1/645

CPC分类号： C12R1/645 ,  C07K7/645 ,  Y10S435/911

摘要： 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.

摘要翻译： PCT No.PCT / KR95 / 00131 Sec。 371日期1997年4月18日 102（e）日期1997年4月18日PCT提交1995年10月16日PCT公布。 公开号WO96 / 12032 日期：1996年04月25日本发明涉及制备具有免疫抑制性质的环孢菌素A生产菌株Tolypocladium inflatum的高效生物质的方法，其中设计用于产生大量环孢菌素A的融合剂KD461的选择为 通过以下步骤获得：开发Tolypocladium inflatum的氨基酸依赖性突变体，从土壤分离的野生菌株，通过UV辐射诱导突变体; 结合L-缬氨酸依赖性和L-亮氨酸依赖突变体，以促进L-缬氨酸和L-亮氨酸，环孢菌素A的前体与有机氮源的需求和效用。 与野生株相比，产生的融合剂KD461具有以下特征：1）在固体麦芽 - 酵母提取物琼脂培养基中生长缓慢，b）菌落的表面为浅灰色，因此比温和菌株更暗 ，c）菌落的背面是深褐色，d）在液体培养基中，它具有短而厚的菌丝与许多关节孢子。