Transcriptional Studies on a Streptomyces clavuligerus oppA2 Deletion Mutant: N -Acetylglycyl-Clavaminic Acid Is an Intermediate of Clavulanic Acid Biosynthesis

Applied and Environmental Microbiology
2018.0

Abstract

<jats:p> The <jats:italic>oppa2</jats:italic> gene encodes an oligopeptide permease essential for the production of clavulanic acid. A transcriptomic analysis of <jats:named-content content-type="genus-species">S. clavuligerus</jats:named-content> Δ <jats:italic>oppA2</jats:italic> :: <jats:italic>aac</jats:italic> in comparison to the parental strain <jats:named-content content-type="genus-species">S. clavuligerus</jats:named-content> ATCC 27064 is reported. The lack of OppA2 results in different expression of 233 genes, including genes for proteases and genes for transport systems. The expression of the clavulanic acid genes in the <jats:italic>oppA2</jats:italic> mutant is not significantly affected, but the genes for holomycin biosynthesis are strongly upregulated, in agreement with the higher holomycin production by this strain. The <jats:italic>oppA2</jats:italic> -mutant is known to release <jats:italic>N</jats:italic> -acetylglycyl-clavaminic acid to the broth. Cosynthesis assays using non-clavulanic acid-producing mutants showed that the addition of pure <jats:italic>N</jats:italic> -acetylglycyl-clavaminic acid to mutants in which clavulanic acid formation was blocked resulted in the recovery of clavulanic acid production, but only in mutants blocked in the early steps of the pathway. This suggests that <jats:italic>N</jats:italic> -acetylglycyl-clavaminic acid is a previously unknown late intermediate of the clavulanic acid pathway.

Knowledge Graph

Similar Paper

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
Mutants of <i>Streptomyces clavuligerus</i> with Disruptions in Different Genes for Clavulanic Acid Biosynthesis Produce Large Amounts of Holomycin: Possible Cross-Regulation of Two Unrelated Secondary Metabolic Pathways
Journal of Bacteriology 2002.0
Morphological differentiation and clavulanic acid formation are affected in a Streptomyces clavuligerus adpA-deleted mutant
Microbiology 2010.0
A pathway‐specific transcriptional activator regulates late steps of clavulanic acid biosynthesis in <i>Streptomyces clavuligerus</i>
Molecular Microbiology 1998.0
Functional analysis of the gene encoding the clavaminate synthase 2 isoenzyme involved in clavulanic acid biosynthesis in Streptomyces clavuligerus
Journal of Bacteriology 1995.0
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
Cloning, sequencing and disruption of a gene from Streptomyces clavuligerus involved in clavulanic acid biosynthesis
Gene 1994.0
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
Clavulanic acid, a β-lactamase inhibitor: biosynthesis and molecular genetics
Applied Microbiology and Biotechnology 2000.0
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