ArticleApplied microbiology and biotechnology2022
Genetic approaches to improve clorobiocin production in Streptomyces roseochromogenes NRRL 3504.
Article in Applied microbiology and biotechnology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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3 citing papers in PubMed, 5 citations in OpenAlex.
- Genome Combination Improvement Strategy Promotes Efficient Spinosyn Biosynthesis inJournal of agricultural and food chemistry · 2025Article
- A metabolomics perspective on clorobiocin biosynthesis: discovery of bromobiocin and novel derivatives through LC-MSMicrobiology spectrum · 2024Article
- The Impact of Heterologous Regulatory Genes from Lipodepsipeptide Biosynthetic Gene Clusters on the Production of Teicoplanin and A40926.Antibiotics (Basel, Switzerland) · 2024Article
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9 authors at 2 institutions in 2 countries.
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Abstract
Streptomyces roseochromogenes NRRL 3504 is best known as a producer of clorobiocin, a DNA replication inhibitor from the aminocoumarin family of antibiotics. This natural product currently draws attention as a promising adjuvant for co-application with other antibiotics against Gram-negative multidrug-resistant pathogens. Herein, we expand the genetic toolkit for NRRL 3504 by showing that a set of integrative and replicative vectors, not tested previously for this strain, could be conjugally transferred at high frequency from Escherichia coli to NRRL 3504. Using this approach, we leverage a cumate-inducible expression of cluster-situated regulatory gene novG to increase clorobiocin titers by 30-fold (up to approximately 200 mg/L). To our best knowledge, this is the highest level of clorobiocin production reported so far. Our findings set a working ground for further improvement of clorobiocin production as well as for the application of genetic methods to illuminate the cryptic secondary metabolome of NRRL 3504. Key Points • Efficient system for conjugative transfer of plasmids into NRRL 3504 was developed. • Expression of regulatory genes in NRRL 3504 led to increase in clorobiocin titer. • Secondary metabolome of NRRL 3504 becomes an accessible target for genetic manipulations using the expanded vector set and improved intergeneric conjugation protocol.
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