Yeast homologous recombination-based promoter engineering for the activation of silent natural product biosynthetic gene clusters.

ABSTRACT: Large-scale sequencing of prokaryotic (meta)genomic DNA suggests that most bacterial natural product gene clusters are not expressed under common laboratory culture conditions. Silent gene clusters represent a promising resource for natural product discovery and the development of a new generation of therapeutics. Unfortunately, the characterization of molecules encoded by these clusters is hampered owing to our inability to express these gene clusters in the laboratory. To address this bottleneck, we have developed a promoter-engineering platform to transcriptionally activate silent gene clusters in a model heterologous host. Our approach uses yeast homologous recombination, an auxotrophy complementation-based yeast selection system and sequence orthogonal promoter cassettes to exchange a

SUBMITTER: Montiel D 

PROVIDER: S-EPMC4517240 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature