An rplKΔ29‐PALG‐32 mutation leads to reduced expression of the regulatory genes ccaR and claR and very low transcription of the ceaS2 gene for clavulanic acid biosynthesis in Streptomyces clavuligerus

Molecular Microbiology
2006.0

Abstract

<jats:title>Summary</jats:title><jats:p>The transcriptional and translational control of the biosynthesis of the β‐lactamase inhibitor clavulanic acid is a subject of great scientific and industrial interest. To study the role of the ribosomal protein L11 on control of clavulanic acid gene transcription, the DNA region <jats:italic>aspC‐tRNA</jats:italic><jats:sup><jats:italic>trp</jats:italic></jats:sup><jats:italic>‐secE‐rplK‐rplA‐rplJ‐rplL</jats:italic> of <jats:italic>Streptomyces clavuligerus</jats:italic> was cloned and characterized. An <jats:italic>S. clavuligerus rplK</jats:italic><jats:sup>ΔPALG</jats:sup> mutant, with an internal 12 nucleotides in‐frame deletion in the <jats:italic>rplK</jats:italic> gene, encoding the L11 (RplK) ribosomal protein lacking amino acids <jats:sup>29</jats:sup>PALG<jats:sup>32</jats:sup>, was constructed by gene replacement. This deletion alters the L11 N‐terminal domain that interacts with the RelA and class I releasing factors‐mediated translational termination. The mutant grew well, showed threefold higher resistance to thiostrepton, did not form spores and lacked diffusible brown pigments, as compared with the wild‐type strain. The wild‐type phenotype was recovered by complementation with the native <jats:italic>rplK</jats:italic> gene. <jats:italic>S. clavuligerus rplK</jats:italic><jats:sup>ΔPALG</jats:sup> produced reduced levels of clavulanic acid (15–26% as compared with the wild type) and cephamycin C (40–50%) in cultures grown in defined SA and complex TSB media. The decreased yields resulted from an impaired transcription of the regulatory genes <jats:italic>ccaR</jats:italic> and <jats:italic>claR</jats:italic> and the <jats:italic>cefD</jats:italic> and <jats:italic>ceaS2</jats:italic> genes for cephamycin and clavulanic acid biosynthesis respectively. Expression of <jats:italic>ceaS2</jats:italic> encoding <jats:styled-content>c</jats:styled-content>arboxy<jats:styled-content>e</jats:styled-content>thyl<jats:styled-content>a</jats:styled-content>rginine <jats:styled-content>s</jats:styled-content>ynthase (CEAS), the precursor‐committing enzyme for clavulanic acid biosynthesis, was particularly affected in this mutant. In the wild‐type strain polyphosphorylated nucleotides peaked at 36–48 h of growth in SA cultures whereas expression of the cephamycin and clavulanic acid genes occurred 12–24 h earlier than the increase in ppGpp indicating that there is no strict correlation between the peak of ppGpp and the onset of transcription of the clavulanic acid and cephamycin C biosynthesis. The drastic effect of the <jats:italic>rplK</jats:italic><jats:sup>ΔPALG</jats:sup> mutation on the onset of expression of the <jats:italic>ceaS2</jats:italic> and the regulatory <jats:italic>ccaR</jats:italic> and <jats:italic>claR</jats:italic> genes and the lack of correlation with ppGpp levels suggest that the onset of transcription of these genes is modulated by the conformational alteration of the N‐terminal region of L11 probably by interaction with the nascent peptide releasing factors and with RelA.

Knowledge Graph

Similar Paper

An <i>rplK</i><sup>Δ29‐PALG‐32</sup> mutation leads to reduced expression of the regulatory genes <i>ccaR</i> and <i>claR</i> and very low transcription of the <i>ceaS2</i> gene for clavulanic acid biosynthesis in <i>Streptomyces clavuligerus</i>
Molecular Microbiology 2006.0
The claR gene of Streptomyces clavuligerus, encoding a LysR-type regulatory protein controlling clavulanic acid biosynthesis, is linked to the clavulanate-9-aldehyde reductase (car) gene
Gene 1998.0
The claR gene of Streptomyces clavuligerus, encoding a LysR-type regulatory protein controlling clavulanic acid biosynthesis, is linked to the clavulanate-9-aldehyde reductase (car) gene
Gene 1998.0
A pathway‐specific transcriptional activator regulates late steps of clavulanic acid biosynthesis in <i>Streptomyces clavuligerus</i>
Molecular Microbiology 1998.0
Morphological differentiation and clavulanic acid formation are affected in a Streptomyces clavuligerus adpA-deleted mutant
Microbiology 2010.0
Characterization of DNA‐binding sequences for CcaR in the cephamycin–clavulanic acid supercluster of <i>Streptomyces clavuligerus</i>
Molecular Microbiology 2011.0
The Pathway-Specific Regulator ClaR of Streptomyces clavuligerus Has a Global Effect on the Expression of Genes for Secondary Metabolism and Differentiation
Applied and Environmental Microbiology 2015.0
Functional analysis of the gene encoding the clavaminate synthase 2 isoenzyme involved in clavulanic acid biosynthesis in Streptomyces clavuligerus
Journal of Bacteriology 1995.0
Proteomics analysis of global regulatory cascades involved in clavulanic acid production and morphological development in<i>Streptomyces clavuligerus</i>
Journal of Industrial Microbiology and Biotechnology 2016.0
Transcriptional Studies on a <i>Streptomyces clavuligerus oppA2</i> Deletion Mutant: <i>N</i> -Acetylglycyl-Clavaminic Acid Is an Intermediate of Clavulanic Acid Biosynthesis
Applied and Environmental Microbiology 2018.0