Heterologous Expression of Novobiocin and Clorobiocin Biosynthetic Gene Clusters

DOI Web Site 被引用文献2件
  • Alessandra S. Eustáquio
    Pharmazeutische Biologie, Pharmazeutisches Institut, Eberhard Karls Universität Tübingen, Auf der Morgenstelle 8, 72076 Tübingen, Germany
  • Bertolt Gust
    Pharmazeutische Biologie, Pharmazeutisches Institut, Eberhard Karls Universität Tübingen, Auf der Morgenstelle 8, 72076 Tübingen, Germany
  • Ute Galm
    Pharmazeutische Biologie, Pharmazeutisches Institut, Eberhard Karls Universität Tübingen, Auf der Morgenstelle 8, 72076 Tübingen, Germany
  • Shu-Ming Li
    Pharmazeutische Biologie, Pharmazeutisches Institut, Eberhard Karls Universität Tübingen, Auf der Morgenstelle 8, 72076 Tübingen, Germany
  • Keith F. Chater
    Department of Molecular Microbiology, John Innes Centre, Norwich Research Park, Colney, Norwich NR4 7UH, United Kingdom
  • Lutz Heide
    Pharmazeutische Biologie, Pharmazeutisches Institut, Eberhard Karls Universität Tübingen, Auf der Morgenstelle 8, 72076 Tübingen, Germany

説明

<jats:title>ABSTRACT</jats:title> <jats:p> A method was developed for the heterologous expression of biosynthetic gene clusters in different <jats:italic>Streptomyces</jats:italic> strains and for the modification of these clusters by single or multiple gene replacements or gene deletions with unprecedented speed and versatility. λ-Red-mediated homologous recombination was used for genetic modification of the gene clusters, and the attachment site and integrase of phage φC31 were employed for the integration of these clusters into the heterologous hosts. This method was used to express the gene clusters of the aminocoumarin antibiotics novobiocin and clorobiocin in the well-studied strains <jats:italic>Streptomyces coelicolor</jats:italic> and <jats:italic>Streptomyces lividans</jats:italic> , which, in contrast to the natural producers, can be easily genetically manipulated. <jats:italic>S. coelicolor</jats:italic> M512 derivatives produced the respective antibiotic in yields comparable to those of natural producer strains, whereas <jats:italic>S. lividans</jats:italic> TK24 derivatives were at least five times less productive. This method could also be used to carry out functional investigations. Shortening of the cosmids' inserts showed which genes are essential for antibiotic production. </jats:p>

収録刊行物

被引用文献 (2)*注記

もっと見る

詳細情報 詳細情報について

問題の指摘

ページトップへ