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Improvement of the enediyne antitumor antibiotic c-1027 production by manipulating its biosynthetic pathway regulation in streptomyces globisporus

Academic Article
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Overview

authors

  • Chen, Y. H.
  • Yin, M.
  • Horsman, G. P.
  • Shen, Ben

publication date

  • March 2011

journal

  • Journal of Natural Products  Journal

abstract

  • The production of C-1027 in Streptomyces globisporus was previously increased 2- to 3-fold by manipulating three pathway-specific activators, SgcR1, SgcR2, and SgcR3. In this study, we have further characterized two putative C-1027 regulatory genes, sgcE1 and sgcR, by in vivo inactivation. The HxlR family DNA-binding protein SgcE1 was not essential for C-1027 biosynthesis, since inactivation of sgcE1 showed no effect on C-1027 production. In contrast, the proposed repressive role of the sgcR gene was confirmed by a 3-fold increase in C-1027 production in the ΔsgcR mutant S. globisporus SB1022 strain relative to the wild-type strain. Considering SgcR shows no significant similarity to any protein of known function, it may be representative of a new family of regulatory proteins. Finally, overexpression of the previously characterized activator sgcR1 in S. globisporus SB1022 increased the C-1027 yield to 37.5 ± 7.7 mg/L, which is about 7-fold higher than the wild-type strain.

subject areas

  • Aminoglycosides
  • Antibiotics, Antineoplastic
  • Base Sequence
  • Biosynthetic Pathways
  • Enediynes
  • Gene Expression Regulation, Bacterial
  • Molecular Structure
  • Streptomyces
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Identity

PubMed Central ID

  • PMC3064734

International Standard Serial Number (ISSN)

  • 0163-3864

Digital Object Identifier (DOI)

  • 10.1021/np100825y

PubMed ID

  • 21250756
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Additional Document Info

start page

  • 420

end page

  • 424

volume

  • 74

issue

  • 3

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