[Roles of geldanamycin biosynthetic genes in Streptomyces hygroscopicus 17997].
Geldanamycin (Gdm), an inhibitor of heat shock protein 90 (Hsp90), shows antitumor and antivirus bioactivity. Most Geldanamycin biosynthetic genes have been cloned from the genome library of Streptomyces hygroscopicus 17997. In this report, polyketide synthase (pks) gene, mono-oxygenase (gdmM) gene and carbamoyltransferase gene (gdmN) were subjected to inactivation. Three gene disrupted mutants (deltapks, deltagdmM and deltagdmN) were obtained by double crossover. No Geldanamycin production was detected in three mutant strains cultured in fermentation broth. Gene complementation experiments excluded the possible polar effect of gene disruption on other genes. These results confirmed that pks, gdmM and gdmN genes were essential for Geldanamycin biosynthesis.
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Key Laboratory of Biotechnology of Antibiotics of Ministry of Health, Beijing 100050, China.
Weiqing
W
He
Yuying
Y
Liu
Guizhi
G
Sun
Yiguang
Y
Wang
D016227:Benzoquinones / Q000378:metabolism*; D019878:Carboxyl and Carbamoyl Transferases / Q000235:genetics; D047029:Lactams, Macrocyclic / Q000378:metabolism*; D006899:Mixed Function Oxygenases / Q000235:genetics; D048630:Polyketide Synthases / Q000235:genetics*; D013302:Streptomyces / Q000235:genetics* / Q000378:metabolism
D016227:Benzoquinones; D047029:Lactams, Macrocyclic; D048630:Polyketide Synthases; D006899:Mixed Function Oxygenases; D019878:Carboxyl and Carbamoyl Transferases; C001277:geldanamycin