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Open AccessJournal ArticleDOI

The dynamic transcriptional and translational landscape of the model antibiotic producer Streptomyces coelicolor A3(2)

TLDR
Nucleotide resolution genome-scale measurements of the transcriptome and translatome of Streptomyces coelicolor, the model antibiotic-producing actinomycete, are integrated and it is revealed that the translation efficiency of secondary metabolic genes is negatively correlated with transcription and that several key antibiotic regulatory genes are translationally induced at transition growth phase.
Abstract
Individual Streptomyces species have the genetic potential to produce a diverse array of natural products of commercial, medical and veterinary interest. However, these products are often not detectable under laboratory culture conditions. To harness their full biosynthetic potential, it is important to develop a detailed understanding of the regulatory networks that orchestrate their metabolism. Here we integrate nucleotide resolution genome-scale measurements of the transcriptome and translatome of Streptomyces coelicolor, the model antibiotic-producing actinomycete. Our systematic study determines 3,570 transcription start sites and identifies 230 small RNAs and a considerable proportion (∼21%) of leaderless mRNAs; this enables deduction of genome-wide promoter architecture. Ribosome profiling reveals that the translation efficiency of secondary metabolic genes is negatively correlated with transcription and that several key antibiotic regulatory genes are translationally induced at transition growth phase. These findings might facilitate the design of new approaches to antibiotic discovery and development.

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Journal ArticleDOI

Recent advances in understanding streptomyces

TL;DR: This review integrates around 100 papers in sections dealing with evolution, ecology, pathogenicity, growth and development, stress responses and secondary metabolism, gene expression, and technical advances of Streptomyces, which are the richest known source of antibiotics.
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Towards systems metabolic engineering in Pichia pastoris

TL;DR: The methylotrophic yeast Pichia pastoris is firmly established as a host for the production of recombinant proteins, frequently outperforming other heterologous hosts, and recent efforts to establish yeast peroxisomes for compartmentalized metabolite synthesis appear to fit ideally with the well-studied high capacity peroxISomal machinery of P. pastoris.
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Adaptive laboratory evolution of a genome-reduced Escherichia coli

TL;DR: Adaptive laboratory evolution is deployed to re-optimise growth performance and show transcriptome and translatome-wide remodeling of the organism that orchestrate metabolism and growth.
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Synthetic biology and metabolic engineering of actinomycetes for natural product discovery.

TL;DR: New advances in reprogramming biosynthetic pathways through polyketide synthase and non-ribosomal peptide synthetase engineering are expected to revitalize discovery and development of new natural products with medicinal and other industrial applications.
Journal ArticleDOI

Omics and multi-omics approaches to study the biosynthesis of secondary metabolites in microorganisms.

TL;DR: This review highlights recent progress in the use and integration of 'omics' approaches with focuses on genomics, transcriptomics, proteomics metabolomics meta-omics and combined omics as powerful strategy to discover new antibiotics.
References
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Journal ArticleDOI

Differential expression analysis for sequence count data.

Simon Anders, +1 more
- 27 Oct 2010 - 
TL;DR: A method based on the negative binomial distribution, with variance and mean linked by local regression, is proposed and an implementation, DESeq, as an R/Bioconductor package is presented.
Journal ArticleDOI

WebLogo: A Sequence Logo Generator

TL;DR: WebLogo generates sequence logos, graphical representations of the patterns within a multiple sequence alignment that provide a richer and more precise description of sequence similarity than consensus sequences and can rapidly reveal significant features of the alignment otherwise difficult to perceive.
Journal ArticleDOI

Genome-Wide Analysis in Vivo of Translation with Nucleotide Resolution Using Ribosome Profiling

TL;DR: A ribosomesome-profiling strategy based on the deep sequencing of ribosome-protected mRNA fragments is presented and enables genome-wide investigation of translation with subcodon resolution and is used to monitor translation in budding yeast under both rich and starvation conditions.
Journal ArticleDOI

The 3′-Terminal Sequence of Escherichia coli 16S Ribosomal RNA: Complementarity to Nonsense Triplets and Ribosome Binding Sites

TL;DR: It is suggested that this region of the RNA is able to interact with mRNA and that the 3'-terminal U-U-A(OH) is involved in the termination of protein synthesis through base-pairing with terminator codons.
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