ArticleApplied and environmental microbiology2006
Engineered biosynthesis of a novel amidated polyketide, using the malonamyl-specific initiation module from the oxytetracycline polyketide synthase.
Article in Applied and environmental microbiology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 122 citations in OpenAlex.
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- Targeted genome mining for microbial antitumor agents acting through DNA intercalation.Synthetic and systems biotechnology · 2023Article
- Magic bullets, magic shields, and antimicrobials in between.Pharmaceutical science advances · 2023Review
- Investigation of diverse biosynthetic secondary metabolites gene clusters using genome mining of indigenousIranian journal of microbiology · 2022Article
- Resistance and phylogeny guided discovery reveals structural novelty of tetracycline antibiotics.Chemical science · 2022Article
- Phylogeny-Informed Synthetic Biology Reveals Unprecedented Structural Novelty in Type V Glycopeptide Antibiotics.ACS central science · 2022Article
- Transcription factor-based biosensors: a molecular-guided approach for natural product engineering.Current opinion in biotechnology · 2021Review
- Quantitative Proteomics Analysis Reveals the Function of the Putative Ester Cyclase UvEC1 in the Pathogenicity of the Rice False Smut FungusInternational journal of molecular sciences · 2021Article
- Molecular Biology Methods in Streptomyces rimosus, a Producer of Oxytetracycline.Methods in molecular biology (Clifton, N.J.) · 2021Article
- The Richness and Diversity of Catalases in Bacteria.Frontiers in microbiology · 2021Article
- Cell-free biosensors for rapid detection of water contaminants.Nature biotechnology · 2020Article
- Biosynthesis of aromatic polyketides in microorganisms using type II polyketide synthases.Microbial cell factories · 2020Review
- Metagenomics Approaches in Discovery and Development of New Bioactive Compounds from Marine Actinomycetes.Current microbiology · 2020Review
- Comparison of Antibiotic Resistance Mechanisms in Antibiotic-Producing and Pathogenic Bacteria.Molecules (Basel, Switzerland) · 2019Review
- Actinomycete-Derived Polyketides as a Source of Antibiotics and Lead Structures for the Development of New Antimicrobial Drugs.Antibiotics (Basel, Switzerland) · 2019Review
- Within-Species Genomic Variation and Variable Patterns of Recombination in the Tetracycline ProducerFrontiers in microbiology · 2019Article
- Lysoquinone-TH1, a New Polyphenolic Tridecaketide Produced by Expressing the Lysolipin Minimal PKS II inAntibiotics (Basel, Switzerland) · 2018Article
- Comparison of Strategies to Overcome Drug Resistance: Learning from Various Kingdoms.Molecules (Basel, Switzerland) · 2018Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Tetracyclines are aromatic polyketides biosynthesized by bacterial type II polyketide synthases (PKSs). Understanding the biochemistry of tetracycline PKSs is an important step toward the rational and combinatorial manipulation of tetracycline biosynthesis. To this end, we have sequenced the gene cluster of oxytetracycline (oxy and otc genes) PKS genes from Streptomyces rimosus. Sequence analysis revealed a total of 21 genes between the otrA and otrB resistance genes. We hypothesized that an amidotransferase, OxyD, synthesizes the malonamate starter unit that is a universal building block for tetracycline compounds. In vivo reconstitution using strain CH999 revealed that the minimal PKS and OxyD are necessary and sufficient for the biosynthesis of amidated polyketides. A novel alkaloid (WJ35, or compound 2) was synthesized as the major product when the oxy-encoded minimal PKS, the C-9 ketoreductase (OxyJ), and OxyD were coexpressed in CH999. WJ35 is an isoquinolone compound derived from an amidated decaketide backbone and cyclized with novel regioselectivity. The expression of OxyD with a heterologous minimal PKS did not afford similarly amidated polyketides, suggesting that the oxy-encoded minimal PKS possesses novel starter unit specificity.
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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.