ArticleNature chemical biology2011
Discovery of parallel pathways of kanamycin biosynthesis allows antibiotic manipulation.
Article in Nature chemical biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 85 citations in OpenAlex.
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- Seq2Saccharide: Discovering Oligosaccharides and Aminoglycosides Natural Products by Integrating Computational Mass Spectrometry and Genome Mining.Journal of the American Chemical Society · 2025Article
- Combinatorial biosynthesis of novel gentamicin derivatives with nonsense mutation readthrough activity and low cytotoxicity.Frontiers in pharmacology · 2025Article
- Glycodiversification of gentamicins throughActa pharmaceutica Sinica. B · 2024Article
- Improving the production of carbamoyltobramycin by an industrial Streptoalloteichus tenebrarius through metabolic engineering.Applied microbiology and biotechnology · 2024Article
- Heterologous production of the D-cycloserine intermediate O-acetyl-L-serine in a human type II pulmonary cell model.Scientific reports · 2023Article
- Facile and selectiveGreen chemistry : an international journal and green chemistry resource : GC · 2022Article
- Characterization and utilization of methyltransferase for apramycin production in Streptoalloteichus tenebrarius.Journal of industrial microbiology & biotechnology · 2022Article
- Engineering ofMolecules (Basel, Switzerland) · 2021Article
- A study on the structure, mechanism, and biochemistry of kanamycin B dioxygenase (KanJ)-an enzyme with a broad range of substrates.The FEBS journal · 2021Article
- Cell-Free Exploration of the Natural Product Chemical Space.Chembiochem : a European journal of chemical biology · 2021Review
- Alteration of the Canine Metabolome After a 3-Week Supplementation of Cannabidiol (CBD) Containing Treats: An Exploratory Study of Healthy Animals.Frontiers in veterinary science · 2021Article
- TheFrontiers in veterinary science · 2021Article
- Establishment of a highly efficient conjugation protocol for Streptomyces kanamyceticus ATCC12853.MicrobiologyOpen · 2019Article
- Complete reconstitution of the diverse pathways of gentamicin B biosynthesis.Nature chemical biology · 2019Article
- Interbacterial mechanisms of colonization resistance and the strategies pathogens use to overcome them.Mucosal immunology · 2019Review
- Comparison of Strategies to Overcome Drug Resistance: Learning from Various Kingdoms.Molecules (Basel, Switzerland) · 2018Review
- Modulation of kanamycin B and kanamycin A biosynthesis in Streptomyces kanamyceticus via metabolic engineering.PloS one · 2017Article
- Parallel pathways in the biosynthesis of aminoglycoside antibiotics.F1000Research · 2017Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Kanamycin is one of the most widely used antibiotics, yet its biosynthetic pathway remains unclear. Current proposals suggest that the kanamycin biosynthetic products are linearly related via single enzymatic transformations. To explore this system, we have reconstructed the entire biosynthetic pathway through the heterologous expression of combinations of putative biosynthetic genes from Streptomyces kanamyceticus in the non-aminoglycoside-producing Streptomyces venezuelae. Unexpectedly, we discovered that the biosynthetic pathway contains an early branch point, governed by the substrate promiscuity of a glycosyltransferase, that leads to the formation of two parallel pathways in which early intermediates are further modified. Glycosyltransferase exchange can alter flux through these two parallel pathways, and the addition of other biosynthetic enzymes can be used to synthesize known and new highly active antibiotics. These results complete our understanding of kanamycin biosynthesis and demonstrate the potential of pathway engineering for direct in vivo production of clinically useful antibiotics and more robust aminoglycosides.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.