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Article
Peptide cyclization catalysed by the thioesterase domain of tyrocidine synthetase
In the biosynthesis of many macrocyclic natural products by multidomain megasynthases, a carboxy-terminal thioesterase (TE) domain is involved in cyclization and product release1,2; however, it has not been deter...
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Article
Biomimetic synthesis and optimization of cyclic peptide antibiotics
Molecules in nature are often brought to a bioactive conformation by ring formation (macrocyclization)1. A recurrent theme in the enzymatic synthesis of macrocyclic compounds by non-ribosomal and polyketide synth...
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Article
TET enzymes, TDG and the dynamics of DNA demethylation
DNA methylation has a profound impact on genome stability, transcription and development. Although enzymes that catalyse DNA methylation have been well characterized, those that are involved in methyl group re...
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Article
Disruption of TET2 promotes the therapeutic efficacy of CD19-targeted T cells
Cancer immunotherapy based on genetically redirecting T cells has been used successfully to treat B cell malignancies1–3. In this strategy, the T cell genome is modified by integration of viral vectors or transpo...
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Article
A vitamin-C-derived DNA modification catalysed by an algal TET homologue
Methylation of cytosine to 5-methylcytosine (5mC) is a prevalent DNA modification found in many organisms. Sequential oxidation of 5mC by ten-eleven translocation (TET) dioxygenases results in a cascade of add...
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Article
Open AccessHigh-performance CRISPR-Cas12a genome editing for combinatorial genetic screening
CRISPR-based genetic screening has revolutionized cancer drug target discovery, yet reliable, multiplex gene editing to reveal synergies between gene targets remains a major challenge. Here, we present a simpl...
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Article
Open AccessModular affinity-labeling of the cytosine demethylation base elements in DNA
5-methylcytosine is the most studied DNA epigenetic modification, having been linked to diverse biological processes and disease states. The elucidation of cytosine demethylation has drawn added attention the ...
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Article
Open AccessExpanded palette of RNA base editors for comprehensive RBP-RNA interactome studies
RNA binding proteins (RBPs) are key regulators of RNA processing and cellular function. Technologies to discover RNA targets of RBPs such as TRIBE (targets of RNA binding proteins identified by editing) and ST...