Publications by authors named "Benjamin M Brandsen"

Antibiotic resistance is a growing threat to public health, making the development of antibiotics of critical importance. One promising class of potential new antibiotics are ribosomally synthesized and post-translationally modified peptides (RiPPs), which include klebsidin, a lasso peptide from that inhibits certain bacterial RNA polymerases. We develop a high-throughput assay based on growth inhibition of to analyze the mutational tolerance of klebsidin.

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Background: The 3' untranslated region (UTR) plays critical roles in determining the level of gene expression through effects on activities such as mRNA stability and translation. Functional elements within this region have largely been identified through analyses of native genes, which contain multiple co-evolved sequence features.

Results: To explore the effects of 3' UTR sequence elements outside of native sequence contexts, we analyze hundreds of thousands of random 50-mers inserted into the 3' UTR of a reporter gene in the yeast Saccharomyces cerevisiae.

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DNAzymes were previously identified by in vitro selection for a variety of chemical reactions, including several biologically relevant peptide modifications. However, finding DNAzymes for peptide lysine acylation is a substantial challenge. By using suitably reactive aryl ester acyl donors as the electrophiles, here we used in vitro selection to identify DNAzymes that acylate amines, including lysine side chains of DNA-anchored peptides.

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Article Synopsis
  • Researchers developed a new method to create biosensors in E. coli that can detect environmental chemicals by stabilizing a transcriptional activator in response to specific ligands.
  • They constructed a biosensor by fusing the lac repressor protein (LacI) to a DNA-binding domain and a transcription-activating domain, achieving a significant 7-fold increase in bacterial growth rate in response to the ligand IPTG.
  • The strategy, which involves mutating the lacI gene and testing its efficacy, was also successfully applied to engineer another protein, MphR, demonstrating its potential for wider use in creating biosensors from natural proteins.
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We describe an unprecedented DNA-catalyzed DNA cleavage process in which a radical-based reaction pathway cleanly results in excision of most atoms of a specific guanosine nucleoside. Two new deoxyribozymes (DNA enzymes) were identified by in vitro selection from N or N random pools initially seeking amide bond hydrolysis, although they both cleave simple single-stranded DNA oligonucleotides. Each deoxyribozyme generates both superoxide (O or HOO) and hydrogen peroxide (HO) and leads to the same set of products (3'-phosphoglycolate, 5'-phosphate, and base propenal) as formed by the natural product bleomycin, with product assignments by mass spectrometry and colorimetric assay.

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Correction for 'DNA-catalyzed glycosylation using aryl glycoside donors' by Anthony R. Hesser et al., Chem.

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We report the identification by in vitro selection of Zn(2+)/Mn(2+)-dependent deoxyribozymes that glycosylate the 3'-OH of a DNA oligonucleotide. Both β and α anomers of aryl glycosides can be used as the glycosyl donors. Individual deoxyribozymes are each specific for a particular donor anomer.

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DNA catalysts (deoxyribozymes) for a variety of reactions have been identified by in vitro selection. However, for certain reactions this identification has not been achieved. One important example is DNA-catalyzed amide hydrolysis, for which a previous selection experiment instead led to DNA-catalyzed DNA phosphodiester hydrolysis.

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Catalyzing the covalent modification of aliphatic amino groups, such as the lysine (Lys) side chain, by nucleic acids has been challenging to achieve. Such catalysis will be valuable, for example, for the practical preparation of Lys-modified proteins. We previously reported the DNA-catalyzed modification of the tyrosine and serine hydroxy side chains, but Lys modification has been elusive.

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We previously reported that DNA catalysts (deoxyribozymes) can hydrolyze DNA phosphodiester linkages, but DNA-catalyzed amide bond hydrolysis has been elusive. Here we used in vitro selection to identify DNA catalysts that hydrolyze ester linkages as well as DNA catalysts that hydrolyze aromatic amides, for which the leaving group is an aniline moiety. The aromatic amide-hydrolyzing deoxyribozymes were examined using linear free energy relationship analysis.

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A new method for the synthesis of β-iodo N-alkenyl 2-pyridones from substituted 2-propargyloxypyridines has been discovered . These compounds present a unique complement of orthogonal functionality and structural characteristics that are unavailable via other routes. The ready access to these compounds renders them an important entry point for the preparation of more complex N-alkyl pyridone-containing targets.

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