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ABSTRACT: Background
Heterologous expression of bacterial biosynthetic gene clusters is currently an indispensable tool for characterizing biosynthetic pathways. Development of an effective, general heterologous expression system that can be applied to bioprospecting from metagenomic DNA will enable the discovery of a wealth of new natural products.Methodology
We have developed a new Escherichia coli-based heterologous expression system for polyketide biosynthetic gene clusters. We have demonstrated the over-expression of the alternative sigma factor ?(54) directly and positively regulates heterologous expression of the oxytetracycline biosynthetic gene cluster in E. coli. Bioinformatics analysis indicates that ?(54) promoters are present in nearly 70% of polyketide and non-ribosomal peptide biosynthetic pathways.Conclusions
We have demonstrated a new mechanism for heterologous expression of the oxytetracycline polyketide biosynthetic pathway, where high-level pleiotropic sigma factors from the heterologous host directly and positively regulate transcription of the non-native biosynthetic gene cluster. Our bioinformatics analysis is consistent with the hypothesis that heterologous expression mediated by the alternative sigma factor ?(54) may be a viable method for the production of additional polyketide products.
SUBMITTER: Stevens DC
PROVIDER: S-EPMC3665592 | biostudies-literature | 2013
REPOSITORIES: biostudies-literature
Stevens David Cole DC Conway Kyle R KR Pearce Nelson N Villegas-Peñaranda Luis Roberto LR Garza Anthony G AG Boddy Christopher N CN
PloS one 20130528 5
<h4>Background</h4>Heterologous expression of bacterial biosynthetic gene clusters is currently an indispensable tool for characterizing biosynthetic pathways. Development of an effective, general heterologous expression system that can be applied to bioprospecting from metagenomic DNA will enable the discovery of a wealth of new natural products.<h4>Methodology</h4>We have developed a new Escherichia coli-based heterologous expression system for polyketide biosynthetic gene clusters. We have de ...[more]