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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
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De Novo Sequencing of Nonribosomal Peptides

2008
While nonribosomal peptides (NRPs) are of tremendous pharmacological importance, there is currently no technology capable of high-throughput sequencing of NRPs. Difficulties in sequencing NRPs slow down the progress in elucidating the non-ribosomal genetic code and negatively affect various screening programs aimed at the discovery of natural compounds
Nuno Bandeira   +5 more
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Pseudoaeruginosins, Nonribosomal Peptides in Nodularia spumigena

ACS Chemical Biology, 2014
Nodularia spumigena is a filamentous cyanobacterium that forms toxic blooms in brackish waters around the world through the production of the pentapeptide toxin nodularin. This cyanobacterium also produces large amounts of protease inhibitors belonging to the aeruginosin and spumigin families. Here we report the discovery of previously unknown protease
Liwei, Liu   +9 more
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Macrocyclization strategies in polyketide and nonribosomal peptide biosynthesis

Natural Product Reports, 2007
AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Florian, Kopp, Mohamed A, Marahiel
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Biosynthetic engineering of nonribosomal peptide synthetases

Journal of Peptide Science, 2016
From the evolutionary melting pot of natural product synthetase genes, microorganisms elicit antibiotics, communication tools, and iron scavengers. Chemical biologists manipulate these genes to recreate similarly diverse and potent biological activities not on evolutionary time scales but within months. Enzyme engineering has progressed considerably in
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