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Biomimetic engineering of nonribosomal peptide synthesis

Biochemical Society Transactions, 2023
Nonribosomal peptides (NRPs) have gained attention due to their diverse biological activities and potential applications in medicine and agriculture. The natural diversity of NRPs is a result of evolutionary processes that have occurred over millions of years.
Kexin Zhang, Hajo Kries
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Biosynthesis of Nonribosomal Peptides

Annual Review of Microbiology, 2004
▪ Abstract  Bacteria and fungi use large multifunctional enzymes, the so-called nonribosomal peptide synthetases (NRPSs), to produce peptides of broad structural and biological activity. Biochemical studies have contributed substantially to the understanding of the key principles of these modular enzymes that can draw on a much larger number of ...
Robert Finking, Mohamed A. Marahiel
openaire   +1 more source

Nonribosomal biosynthesis of backbone-modified peptides

Nature Chemistry, 2017
Biosynthetic modification of nonribosomal peptide backbones represents a potentially powerful strategy to modulate the structure and properties of an important class of therapeutics. Using a high-throughput assay for catalytic activity, we show here that an L-Phe-specific module of an archetypal nonribosomal peptide synthetase can be reprogrammed to ...
David L. Niquille   +5 more
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Combinatorial biosynthesis of polyketides and nonribosomal peptides

Current Opinion in Chemical Biology, 2001
The engineering of polyketide biosynthesis has begun to provide robust targeted libraries for screening against pharmaceutically relevant targets. New technologies that offer methodology for the rapid generation of more structurally diverse libraries have now been demonstrated.
J, Staunton, B, Wilkinson
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Nonribosomal peptide synthetases: structures and dynamics

Current Opinion in Structural Biology, 2010
Nonribosomal peptide synthetases (NRPSs) are large multimodular biocatalysts that utilize complex regiospecific and stereospecific reactions to assemble structurally and functionally diverse peptides that have important medicinal applications. During this ribosome-independent peptide synthesis, catalytic domains of NRPS select, activate or modify the ...
Matthias, Strieker   +2 more
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FRET monitoring of a nonribosomal peptide synthetase

Nature Chemical Biology, 2017
Nonribosomal peptide synthetases (NRPSs) are multidomain enzyme templates for the synthesis of bioactive peptides. Large-scale conformational changes during peptide assembly are obvious from crystal structures, yet their dynamics and coupling to catalysis are poorly understood.
Jonas Alfermann   +8 more
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A Practical Guideline to Engineering Nonribosomal Peptide Synthetases

2023
The bioengineering of nonribosomal peptide synthetases (NRPSs) is a rapidly developing field to access natural product derivatives and new-to-nature natural products like scaffolds with changed or improved properties. However, the rational (re-)design of these often gigantic assembly-line proteins is by no means trivial and needs in-depth insights into
Abbood, N.   +3 more
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Free Piperazic Acid as a Precursor to Nonribosomal Peptides

Journal of the American Chemical Society, 2022
Piperazic acid (Piz) is a nonproteinogenic amino acid possessing a rare nitrogen-nitrogen bond. However, little is known about how Piz is incorporated into nonribosomal peptides, including whether adenylation domains specific to Piz exist. In this study, we show that free piperazic acid is directly adenylated and then incorporated into the ...
Zi-Wang Wei   +5 more
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Metagenome Driven Discovery of Nonribosomal Peptides

ACS Chemical Biology, 2019
Declining rates of novel natural product discovery and exponential rates of rediscovery heralded the end of the 1940s to 1960s "golden era" of antibiotic discovery. Fifty years later, the implementation of molecular screening methodologies revealed that standard culture-based screening approaches had failed to capture the vast majority of environmental
Luke J. Stevenson   +2 more
openaire   +2 more sources

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