ArticleProceedings of the National Academy of Sciences of the United States of America2010
Reverse biological engineering of hrdB to enhance the production of avermectins in an industrial strain of Streptomyces avermitilis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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44 citing papers in PubMed, 95 citations in OpenAlex.
- Actinobacteria TFDB: An integrated view of transcription factors in Actinobacteria.Engineering microbiology · 2026Article
- A noncanonical transcriptional regulation in natural product biosynthesis.Nucleic acids research · 2026Article
- Molecular basis of Streptomyces ECF σShbA factors transcribing principal σHrdB genes.Nucleic acids research · 2025Article
- Improving polyketide biosynthesis by rescuing the translation of truncated mRNAs into functional polyketide synthase subunits.Nature communications · 2025Article
- Sigma Factor Engineering inMicroorganisms · 2024Article
- Influence of Cluster-Situated Regulator PteF in Filipin Biosynthetic Cluster on Avermectin Biosynthesis inBiology · 2024Article
- Co-Expression of Transcriptional Regulators and Housekeeping Genes inMicroorganisms · 2023Article
- Applications of synthetic biology in medical and pharmaceutical fields.Signal transduction and targeted therapy · 2023Review
- Rethinking Biosynthesis of Aclacinomycin A.Molecules (Basel, Switzerland) · 2023Review
- CRISPR/Cas9-Mediated Multi-Locus Promoter Engineering inMicroorganisms · 2023Article
- Zinc-Responsive Regulator Zur Regulates Zinc Homeostasis, Secondary Metabolism, and Morphological Differentiation in Streptomyces avermitilis.Applied and environmental microbiology · 2022Article
- Activating cryptic biosynthetic gene cluster through a CRISPR-Cas12a-mediated direct cloning approach.Nucleic acids research · 2022Article
- Characterization of Streptomyces sp. LS462 with high productivity of echinomycin, a potent antituberculosis and synergistic antifungal antibiotic.Journal of industrial microbiology & biotechnology · 2021Article
- Article
- Mining and fine-tuning sugar uptake system for titer improvement of milbemycins inSynthetic and systems biotechnology · 2020Article
- Genome-based mining of new antimicrobial meroterpenoids from the phytopathogenic fungus Bipolaris sorokiniana strain 11134.Applied microbiology and biotechnology · 2020Article
- Harnessing the intracellular triacylglycerols for titer improvement of polyketides in Streptomyces.Nature biotechnology · 2020Article
- The Application of Regulatory Cascades inFrontiers in microbiology · 2020Review
- Phosphate limitation increases coenzyme QSynthetic and systems biotechnology · 2019Article
- Recent advances in natural products exploitation inEngineering in life sciences · 2019Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Avermectin and its analogues are produced by the actinomycete Streptomyces avermitilis and are widely used in the field of animal health, agriculture, and human health. Here we have adopted a practical approach to successfully improve avermectin production in an industrial overproducer. Transcriptional levels of the wild-type strain and industrial overproducer in production cultures were monitored using microarray analysis. The avermectin biosynthetic genes, especially the pathway-specific regulatory gene, aveR, were up-regulated in the high-producing strain. The upstream promoter region of aveR was predicted and proved to be directly recognized by sigma(hrdB) in vitro. A mutant library of hrdB gene was constructed by error-prone PCR and selected by high-throughput screening. As a result of evolved hrdB expressed in the modified avermectin high-producing strain, 6.38 g/L of avermectin B1a was produced with over 50% yield improvement, in which the transcription level of aveR was significantly increased. The relevant residues were identified to center in the conserved regions. Engineering of the hrdB gene can not only elicit the overexpression of aveR but also allows for simultaneous transcription of many other genes. The results indicate that manipulating the key genes revealed by reverse engineering can effectively improve the yield of the target metabolites, providing a route to optimize production in these complex regulatory systems.
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