NOVEL ANSAMYCIN DERIVATIVES AND THE METHOD FOR MUTATIONAL BIOSYNTHESIS THEREOF

摘要

A method for producing new ansamycin derivatives by using 3-amino-5-hydroxylbenzoic acid(AHBA) is provided to inhibit Hsp90(heat shock protein 90) similar to geldanamycin, so that the derivatives are useful as antibiotic, antifungal agent, antiviral agent, immunosuppressant, anti-inflammatory agent, degenerative nerve disease-treating agent and anticancer agent. A method for producing new ansamycin derivatives comprises the steps of: (1) preparing an AHBA biosynthesis gene-inactivated construct; (2) preparing a recombinant vector containing the construct; (3) transforming a host cell with the recombinant vector to prepare recombinant cell; and (4) culturing the recombinant cell in a medium containing AHBA or its analogues, wherein the AHBA biosynthesis gene is napK gene having the nucleotide sequence of SEQ ID NO:7; and the host cell is Streptomyces hygroscopicus var. geldanus NRRL 3602 or Streptomyces melanosporofaciens. Further, the Streptomyces melanosporofaciens is Streptomyces hygroscopicus subsp. duamyceticus or Streptomyces hygroscopicus 17997.