公开(公告)号：US20050003409A1

公开(公告)日：2005-01-06

申请号：US10844716

申请日：2004-05-13

Applicant: Chengjin Huang ,  Deborah Chaleff ,  Mark Ruppen ,  Jerome Stephens

Inventor： Chengjin Huang ,  Deborah Chaleff ,  Mark Ruppen ,  Jerome Stephens

IPC: C12N15/09 ,  A61K31/7048 ,  A61P31/04 ,  C12N1/21 ,  C12N9/02 ,  C12N9/10 ,  C12N9/16 ,  C12N15/31 ,  C12N15/52 ,  C12N15/53 ,  C12N15/54 ,  C12N15/55 ,  C12P17/18 ,  C12R1/465 ,  C12Q1/68 ,  C07H21/04 ,  C12N9/88 ,  C12N15/74 ,  C12P19/60

CPC classification number: C12N9/0004 ,  C12N9/1007 ,  C12N9/16 ,  C12N15/52 ,  C12P17/181

Abstract: The present invention relates to the complete biosynthetic pathway for the formation of the LL-F28249 compounds and, most importantly, the major component LL-F28249α. The purified and isolated nucleic acid molecule encoding the proteins of the biosynthetic pathway, which is isolated from a wild-type or mutant Streptomyces, is fully described in FIG. 6 to FIG. 6-39and SEQ ID NO:1. The DNA gene cluster and its expression in a suitable host enable the efficient production of the highly active natural metabolites and semisynthetic derivatives. The invention further concerns plasmids, vectors and host cells that contain and express the novel nucleic acid molecule. Of particular interest, the entire biosynthetic pathway fits compactly in three plasmids, Cos11, Cos36 and Cos40. The invention also concerns the purified and isolated biosynthesis proteins that are encoded by the whole DNA gene cluster. Additionally, the invention involves a new efficient, biochemical method of preparing moxidectin.

Abstract translation: 本发明涉及用于形成LL-F28249化合物的完整生物合成途径，最重要的是涉及主要成分LL-F28249α。 编码从野生型或突变链霉菌分离的生物合成途径的蛋白质的纯化和分离的核酸分子在图1中完全描述。 参照图6〜 6-39和SEQ ID NO：1。 DNA基因簇及其在合适的宿主中的表达使得能够高效生产高活性的天然代谢物和半合成衍生物。 本发明还涉及含有和表达新型核酸分子的质粒，载体和宿主细胞。 特别令人感兴趣的是，整个生物合成途径紧密地适应于三种质粒Cos11，Cos36和Cos40。 本发明还涉及由整个DNA基因簇编码的纯化和分离的生物合成蛋白。 此外，本发明涉及制备莫昔克丁的新的有效的生物化学方法。