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Genes for production of the enediyne antitumor antibiotic c-1027 in streptomyces globisporus are clustered with the caga gene that encodes the c-1027 apoprotein

Academic Article
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Overview

authors

  • Liu, W.
  • Shen, Ben

publication date

  • February 2000

journal

  • Antimicrobial Agents and Chemotherapy  Journal

abstract

  • C-1027, the most potent member of the enediyne antitumor antibiotic family, is produced by Streptomyces globisporus C-1027 and consists of an apoprotein (encoded by the cagA gene) and a nonpeptidic chromophore. The C-1027 chromophore could be viewed as being derived biosynthetically from a benzoxazolinate, a deoxyamino hexose, a beta-amino acid, and an enediyne core. By adopting a strategy for cloning of the C-1027 biosynthesis gene cluster by mapping a putative dNDP-glucose 4,6-dehydratase (NGDH) gene to cagA, we have localized 75 kb of contiguous DNA from S. globisporus. DNA sequence analysis of two regions of the cloned gene cluster revealed two genes, sgcA and sgcB, that encode an NGDH enzyme and a transmembrane efflux protein, respectively, and confirmed that the cagA gene resides approximately 14 kb upstream of the sgcAB locus. The involvement of the cloned gene cluster in C-1027 biosynthesis was demonstrated by disrupting the sgcA gene to generate C-1027-nonproducing mutants and by complementing the sgcA mutants in vivo to restore C-1027 production. These results represent the first cloning of a gene cluster for enediyne antitumor antibiotic biosynthesis and provide a starting point for future genetic and biochemical investigations of C-1027 biosynthesis.

subject areas

  • Amino Acid Sequence
  • Aminoglycosides
  • Anti-Bacterial Agents
  • Antibiotics, Antineoplastic
  • Antigens, Bacterial
  • Bacterial Proteins
  • Base Sequence
  • Chromosome Mapping
  • Chromosomes, Bacterial
  • DNA, Bacterial
  • Enediynes
  • Fungal Proteins
  • Genetic Complementation Test
  • Hydro-Lyases
  • Membrane Proteins
  • Molecular Sequence Data
  • Multienzyme Complexes
  • Multigene Family
  • Polymerase Chain Reaction
  • Sequence Homology, Amino Acid
  • Streptomyces
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Identity

International Standard Serial Number (ISSN)

  • 0066-4804

Digital Object Identifier (DOI)

  • 10.1128/aac.44.2.382-392.2000

PubMed ID

  • 10639366
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Additional Document Info

start page

  • 382

end page

  • 392

volume

  • 44

issue

  • 2

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