Verification on the Function of Geldanamycin Biosynthetic Genes in Streptomyces hygroscopicus 17997

Geldanamycin (Gdm), as inhibitor of heat shock protein 90 (Hsp90), shows antitumor and antivirus bioactivity. Most of Gdm biosynthetic genes have been cloned from the genome library of S. hygroscopicus 17997. In this report, polyketide synthase (pks) gene, monooxygenase (gdmM) gene, and carbamoyltransferase gene (gdmN) were subjected to inactivation, respectively. Three gene disrupted mutants (Δpks, ΔgdmM, and ΔgdmN) were obtained by double crossover. No Gdm 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 Gdm biosynthesis.