ArticleChemistry & biology2015
Iterative Mechanism of Macrodiolide Formation in the Anticancer Compound Conglobatin.
Article in Chemistry & biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
35 citing papers in PubMed, 78 citations in OpenAlex.
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- Natural Occurrence of Hybrid Polyketides from Two Distinct Biosynthetic Pathways inACS chemical biology · 2021Article
- Comparative Metabologenomics Analysis of Polar Actinomycetes.Marine drugs · 2021Article
- Recent Advances in Silent Gene Cluster Activation inFrontiers in bioengineering and biotechnology · 2021Review
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- Biosynthesis of depsipeptides, or Depsi: The peptides with varied generations.Protein science : a publication of the Protein Society · 2020Review
- Conglobatins B-E: cytotoxic analogues of the CThe Journal of antibiotics · 2020Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Conglobatin is an unusual C2-symmetrical macrodiolide from the bacterium Streptomyces conglobatus with promising antitumor activity. Insights into the genes and enzymes that govern both the assembly-line production of the conglobatin polyketide and its dimerization are essential to allow rational alterations to be made to the conglobatin structure. We have used a rapid, direct in vitro cloning method to obtain the entire cluster on a 41-kbp fragment, encoding a modular polyketide synthase assembly line. The cloned cluster directs conglobatin biosynthesis in a heterologous host strain. Using a model substrate to mimic the conglobatin monomer, we also show that the conglobatin cyclase/thioesterase acts iteratively, ligating two monomers head-to-tail then re-binding the dimer product and cyclizing it. Incubation of two different monomers with the cyclase produces hybrid dimers and trimers, providing the first evidence that conglobatin analogs may in future become accessible through engineering of the polyketide synthase.
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Registered trials
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.