Identification of AHBA Biosynthetic Genes Related to Geldanamycin Biosynthesis in Streptomyces hygroscopicus 17997 |
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Authors: | Weiqing He Linzhuan Wu Qunjie Gao Yu Du Yiguang Wang |
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Institution: | (1) Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Peking Union Medical College, Tiantan Xili No 1, Beijing, 100050, China |
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Abstract: | To clone and study the geldanamycin biosynthetic gene cluster in Streptomyces hygroscopicus 17997, we designed degenerate primers based on the conserved sequence of the ansamycin 3-amino-5-hydroxybenzoic acid (AHBA)
synthase gene. A 755-bp polymerase chain reaction product was obtained from S. hygroscopicus 17997 genomic DNA, which showed high similarity to ansamycin AHBA synthase genes. Through screening the cosmid library of
S. hygroscopicus 17997, two loci of separated AHBA biosynthetic gene clusters were discovered. Comparisons of sequence homology and gene organization
indicated that the two AHBA biosynthetic gene clusters could be divided into a benzenic and a naphthalenic subgroup. Gene
disruption demonstrated that the benzenic AHBA gene cluster is involved in the biosynthesis of geldanamycin. However, the
naphthalenic AHBA genes in the genome of Streptomyces hygroscopicus 17997 could not complement the deficiency of the benzenic AHBA genes. This is the first report on the AHBA biosynthetic gene
cluster in a geldanamycin-producing strain.
W. He and L. Wu contributed equally to this work. |
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