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    • 3. 发明申请
    • NRPS-PKS GENE CLUSTER AND ITS MANIPULATION AND UTILITY
    • NRPS-PKS基因簇及其操纵和实现
    • WO2009115822A1
    • 2009-09-24
    • PCT/GB2009/000759
    • 2009-03-20
    • SINVENT ASZOTCHEV, SergeyJØRGENSEN, HanneSLETTA, HavardELLINGSEN, Trond, ErlingFJAERVIK, EspenDEGNES, Kristin, FløgstadKLINKENBERG, GeirBRUHEIM, PerDZIEGLEWSKA, Hanna Eva
    • ZOTCHEV, SergeyJØRGENSEN, HanneSLETTA, HavardELLINGSEN, Trond, ErlingFJAERVIK, EspenDEGNES, Kristin, FløgstadKLINKENBERG, GeirBRUHEIM, Per
    • C07K14/36C12N15/52C12N1/20C07G11/00
    • C12N15/52C07D225/02C07K14/36C12P17/10C12P19/62C12R1/465
    • The present invention provides a nucleic acid molecule comprising: (a) a nucleotide sequence as shown in SEQ ID No. 1; or (b) a nucleotide sequence which is the complement of SEQ ID No. 1; or (c) a nucleotide sequence which is degenerate with SEQ ID No. 1; or (d) a nucleotide sequence having at least 85% sequence identity (preferably at least 87%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity) with SEQ ID No. 1; or (e) a part of any one of (a) to (d), wherein said nucleic acid molecule encodes or is a complementary to a nucleic acid molecule encoding one or more polypeptides, or comprises or is complementary to a nucleic acid molecule comprising one or more genetic elements, having functional activity in the synthesis of a polyketide-based or macrolactam molecule. Particularly the invention contemplates the modification of the nucleic acid of the invention, encoding the biosynthetic machinery for the synthesis of the polyketide macrolactam BE- 14106, including expressing in a microorganism the modified nucleic acid molecule. In certain aspects the modification includes introducing, mutating, deleting, replacing or inactivating a sequence encoding one or more activities or proteins encoded by said nucleic acid molecule. Other aspects of the invention include a microorganism containing the modified and unmodified nucleic acid and recovering the polyketide-based or macrolactam molecule from said mircoorganism.
    • 本发明提供了一种核酸分子,其包含:(a)SEQ ID No.1所示的核苷酸序列; 或(b)作为SEQ ID No.1的互补序列的核苷酸序列; 或(c)与SEQ ID No.1退行的核苷酸序列; 或(d)具有至少85%序列同一性(优选至少87%,90%,91%,92%,93%,94%,95%,96%,97%,98%或99% 序列同一性); 或(e)(a)至(d)中任一项的一部分,其中所述核酸分子编码或与编码一种或多种多肽的核酸分子互补,或包含或互补于包含 一种或多种在合成聚酮化合物或大内酰胺分子中具有功能活性的遗传元件。 特别地,本发明考虑了本发明的核酸的修饰,其编码用于合成聚酮化合物大内酰胺BE-14106的生物合成机理,包括在微生物中表达经修饰的核酸分子。 在某些方面,修饰包括引入,突变,缺失,替换或失活编码由所述核酸分子编码的一种或多种活性或蛋白质的序列。 本发明的其它方面包括含有经修饰和未修饰的核酸的微生物,并从所述微生物中回收聚酮化合物或大环内酰胺分子。