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Engineered production of iso-migrastatin in heterologous streptomyces hosts

Academic Article
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Overview

authors

  • Feng, Z. Y.
  • Wang, L. Y.
  • Rajski, S. R.
  • Xu, Z. N.
  • Coeffet-LeGal, M. F.
  • Shen, Ben

publication date

  • March 2009

journal

  • Bioorganic & Medicinal Chemistry  Journal

abstract

  • Glutarimide-containing polyketides such as migrastatin (MGS) are well known for their ability to inhibit tumor cell migration. We have previously shown that MGS is derived from iso-migrastatin (iso-MGS) via a H(2)O-mediated ring-expansion rearrangement. A bacterial artificial chromosome (BAC) library of Streptomyces platensis NRRL18993, an iso-MGS producer, was constructed. From this library, pBS11001, a BAC clone harboring the intact iso-MGS biosynthetic gene cluster, was identified. Mobilization of pBS11001 into five heterologous Streptomyces hosts afforded recombinant strains, SB11001, SB11002, SB11003, SB11004, and SB11005, respectively. Under a standard set of media and fermentation conditions, the recombinant strains all produced the same profile of iso-MGS as that of S. platensis NRRL18993. These findings highlight the strength and flexibility of the BAC-based technology for natural product production and engineering in heterologous Streptomyces model hosts.

subject areas

  • Base Sequence
  • Chromatography, High Pressure Liquid
  • Chromatography, Liquid
  • Chromosomes, Artificial, Bacterial
  • Cloning, Molecular
  • DNA Primers
  • Macrolides
  • Mass Spectrometry
  • Multigene Family
  • Piperidones
  • Polymerase Chain Reaction
  • Streptomyces
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Identity

PubMed Central ID

  • PMC3075207

International Standard Serial Number (ISSN)

  • 0968-0896

Digital Object Identifier (DOI)

  • 10.1016/j.bmc.2008.10.074

PubMed ID

  • 19010685
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Additional Document Info

start page

  • 2147

end page

  • 2153

volume

  • 17

issue

  • 6

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