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Symbiosis-inspired approaches to antibiotic discovery.
TLDR
It is contended that symbioses provide almost unlimited opportunities for the discovery of new bioactive compounds whose activities and applications have been evolutionarily optimized and the possibility that environmental effectors can guide laboratory expression of secondary metabolites from "orphan", or silent, biosynthetic gene clusters (BGCs). Expand
Design, Synthesis, and Preliminary Biological Evaluation of a DNA Methyltransferase‐Directed Alkylating Agent
TLDR
A novel N-mustard is synthesized that probably proceeds (under biological conditions) to the aziridinium ion 2, a structure highly homologous with SAM, and a new cofactor mimic is found to be remarkably efficient at MTase-driven DNA alkylation. Expand
Functional characterization of TtnD and TtnF, unveiling new insights into tautomycetin biosynthesis.
TLDR
New analogues resulting from inactivation of two genes, ttnD and ttnF, in S. griseochromogenes are produced and characterized, revealing the importance of the functional groups installed by TtnDF and the C2''-C5 fragment of TTN to be a critical structural determinant behind the important and unique PP-1 selectivity displayed by TTN. Expand
Dedicated ent-kaurene and ent-atiserene synthases for platensimycin and platencin biosynthesis
TLDR
The PTM and PTN biosynthetic machineries provide a rare glimpse at how secondary metabolic pathway evolution increases natural product structural diversity and support the wisdom of applying combinatorial biosynthesis methods for the generation of novel P TM and/or PTN analogues, thereby facilitating drug development efforts based on these privileged natural product scaffolds. Expand
In situ generation of a bisubstrate analogue for protein arginine methyltransferase 1.
TLDR
Using the approach outlined in this communication, it should be possible to generate bisubstrate analogue-based inhibitors of PRMT isozymes that are potent and highly selective for a particular isozyme. Expand
DNA repair: models for damage and mismatch recognition.
TLDR
Current models for how DNA damage recognition may occur and the chemical characteristics, shared by damaged DNA sites, of which repair proteins may take advantage are discussed. Expand
Conversion of DNA methyltransferases into azidonucleosidyl transferases via synthetic cofactors
TLDR
The conversion of biological methyltransferases into azidonucleosidyl transferases demonstrated here also holds tremendous promise as a means of identifying, as yet, unknown substrates of methylation. Expand
Expression of the platencin biosynthetic gene cluster in heterologous hosts yielding new platencin congeners.
TLDR
E engineered production of PTN and congeners in a model Streptomyces host provides new opportunities to apply combinatorial biosynthetic strategies to the PTN biosynthesis machinery for structural diversity. Expand
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