ArticleJournal of industrial microbiology & biotechnology2019
Improved production of clavulanic acid by reverse engineering and overexpression of the regulatory genes in an industrial Streptomyces clavuligerus strain.
Article in Journal of industrial microbiology & biotechnology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 14 citations in OpenAlex.
- Unlocking the Bioactive Potential of Streptomyces: A Multidisciplinary Approach to Strain Improvement.MicrobiologyOpen · 2026Review
- Integrated genomic-transcriptomic analysis of clavulanic acid production in differentially productive Streptomyces clavuligerus strains.Scientific reports · 2025Article
- Regulation and induction of fungal secondary metabolites: a comprehensive review.Archives of microbiology · 2025Review
- Genomic Diversity ofInternational journal of molecular sciences · 2024Article
- Transcriptome profiles of Streptomyces clavuligerus strains producing different titers of clavulanic acid.Scientific data · 2023Article
- Re-classification ofiScience · 2021Article
- Enhanced production of clavulanic acid by improving glycerol utilization using reporter-guided mutagenesis of an industrial Streptomyces clavuligerus strain.Journal of industrial microbiology & biotechnology · 2021Article
- Clavulanic Acid Production byAntibiotics (Basel, Switzerland) · 2021Review
- Comparative Genomics Determines Strain-Dependent Secondary Metabolite Production inBiomolecules · 2020Article
- Coordinated regulation for nature products discovery and overproduction inSynthetic and systems biotechnology · 2020Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 1 country.
Funding
Abstract
Genomic analysis of the clavulanic acid (CA)-high-producing Streptomyces clavuligerus strains, OL13 and OR, developed through random mutagenesis revealed a frameshift mutation in the cas1 gene-encoding clavaminate synthase 1. Overexpression of the intact cas1 in S. clavuligerus OR enhanced the CA titer by approximately 25%, producing ~ 4.95 g/L of CA, over the OR strain in the flask culture. Moreover, overexpression of the pathway-specific positive regulatory genes, ccaR and claR, in the OR strain improved CA yield by approximately 43% (~ 5.66 g/L) in the flask. However, co-expression of the intact cas1 with ccaR-claR did not further improve CA production. In the 7 L fermenter culture, maximum CA production by the OR strain expressing the wild-type cas1 and ccaR-claR reached approximately 5.52 g/L and 6.01 g/L, respectively, demonstrating that reverse engineering or simple rational metabolic engineering is an efficient method for further improvement of industrial strains.
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Registered trials
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