Geldanamycin Bacteria Streptomyces Hygroscopicus 17997 In Ansa Class Of Antibiotic Biosynthesis Gene Cluster Cloning And Research

Ansamycins are a class of natural compounds produced by a variety of microorganisms and plants. Structurally they are characterized by a macrocycle composed of an aromatic ring system by an polyketide chain that forms an amide linkage to the amino group of the aromatic moiety. Based on the structure of the aromatic moiety, this family of compounds can be further subdivided into a benzenic and a naphthalenic subgroup. 3-amino-5-hydroxybenzoic acid(AHBA), the common starter unit for the biosynthesis of ansamycins , is a novel variant of the shikimate pathway.Streptomyces hygroscopicus17997 was identified as a geldanamycin, benzenic ansamycin, producer from a Chinese soil isolation. Geldanamycin inhibits the expression of oncogene in vivo and in vitro. It also affects the hot shock protein 90 (Hsp90)by binding specifically with it. The broad antiviral activity of geldanamycin besides its antitumor activity was discovered by our Institute. Studies on the geldanamycin biosynthetic genes from Streptomyces hygroscopicus17997 may provide some clues to understanding the mechanism of geldanamycin biosynthesis and facilitate the further modification of its structure. Although the precursors of ansamycin, AHBA, had been identified, very little was known about the biosynthetic gene clusters responsible for geldanamycin.A genomic library from the strain17997 was constructed from large (20-30kb) fragments of total DNA with pKC505, a E.coli/Streptomyces shuttle cosmid vector. The percentage of recombinant cosmids in constructed library was estimated and the coverage of genome was complete as about 99.99%.The...