Global ETD Search
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Showing 1 to 20 of 39 for “"ribosomally-synthesized and post-translationally modified"”.
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Discovery and characterization of ribosomally synthesized and post-translationally modified peptide natural products
… rise in antibiotic- resistant pathogens. Ribosomally synthesized and post-translationally modified peptide (RiPP) natural products are genetically encoded peptide-derived secondary metabolites whose structures can be predicted based on gene sequence and identity of tailoring enzymes within …
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On the biosynthesis and discovery of ribosomally synthesized and post-translationally modified peptides
Thiazole/oxazole-modified microcins (TOMMs) comprise a family of ribosomally synthesized and post-translationally modified peptides (RiPPs) that all contain thiazole and oxazole heterocycles derived from cysteine, serine, and threonine residues, respectively. The thiazole/oxazole heterocycle is …
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Biosynthesis and mode of action of ribosomally synthesized and post-translationally modified antimicrobial peptides
… compounds serve as platforms for the design and development of novel drugs and therapeutics. The overwhelming amount of genomic information acquired in recent years has revealed that ribosomally synthesized and post-translationally modified natural products are much more widespread than …
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Development of a synthetic biology platform to discover novel ribosomally synthesized and post-translationally modified peptides
Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2026-12-01
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Mechanistic interrogations of ribosomal and non-ribosomal natural product enzymes
… herein is my thesis work towards structural and biochemical characterization of bacterial proteins involved in metabolite regulation and natural product biosynthesis. In the first case, I will describe the structural basis for transcriptional regulation of a small molecule metabolite, …
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Development Towards an Ethylene Sensing Artificial Metalloenzyme
… ripening hormone for climacteric plants, and consequently its detection and quantification is of considerable interest to the horticulture industry. Its detection however is a non-trivial pursuit, traditionally requiring expensive and inaccessible instrumentation that fail to provide in …
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Discovery and structural characterization of lanthipeptides from soil and rumen bacteria
As members of the ribosomally synthesized and post-translationally modified peptide natural products (RiPPs), lanthipeptides possess myriad structural diversity and potential for discovery using genome-guided approaches. Biological activities of interest embedded within lanthipeptide structures …
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Characterization of Cyclopropyl Synthases Involved in the Maturation of Ribosomally Synthesized and Posttranslationally Modified Peptides
<p>Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a large class of natural products with significant human health implications. RiPPs are synthesized from a genetically encoded precursor peptide that undergoes significant modifications by maturing enzymes, or …
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Development of lanthipeptide engineering strategies
… compounds. The lanthipeptides, members of the ribosomally synthesized and post-translationally modified peptide class of natural products, have potential applications ranging from clinical imaging to cystic fibrosis treatment. Additionally, many lanthipeptides possess strong antimicrobial …
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Functional and mechanistic elucidation of peptide backbone thioamidation
… the ATP-dependent peptide backbone activation and subsequent formation of azoline heterocycles. It has been proposed that YcaO enzymes can also install lactamidines and thioamides onto peptides through similar mechanisms. These modifications are found in a class of natural products named …
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Biochemical characterization of enzymes involved in the biosynthesis of the thiopeptide thiomuracin
… modes of action. Thiopeptides are a family of ribosomally synthesized and post-translationally modified peptides (RiPPs) that have outstanding biological profile, including high potency against a variety of antibiotic resistant pathogenic strains. Their new modes of action have attracted many …
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Expanding the structural diversity of the RiPP class of natural products
Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a diverse and rapidly expanding class of natural products. Despite starting out as linear chains of amino acids, RiPP natural products acquire structural diversity ranging from small molecules like microcin C7 to 48-mer …
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Design of Post-Translationally Modified Peptides by Combining Enzymes from Diverse Pathways
Over the past decade, ribosomally-synthesized and post-translationally modified peptides (RiPPs) have emerged as both therapeutically-relevant and engineerable, two traits previously unobserved together in a natural product class. Their biosynthesis is modular: a precursor peptide recruits enzymes …
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Investigation of the Lacticin 481 Synthetase and Its Substrate LctA in the Production of the Antibiotic Lacticin 481
Lantibiotics are ribosomally synthesized and post-translationally modified peptide antimicrobial agents produced by Gram-positive bacteria that contain thioether cross-links termed lanthionines. Lantibiotic biosynthesis begins with a precursor peptide (LanA) consisting of leader and propeptide …
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Structural studies of S-adenosyl-L-methionine radical enzymes involved in tRNA and natural product biosynthesis
… enzyme superfamily catalyze a myriad of diverse and challenging biotransformations using a [4Fe-4S] cluster and a molecule of AdoMet to initiate radical. In this thesis, we used a combination of crystallographic and biochemical methods to identify the use of covalent catalysis and polar reactions …
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Engineering of the microviridin post-translational modification enzymes for the production of synthetic protease inhibitors
Natural products and their derivatives have always been a source of drug leads. In particular, bacterial compounds have played an important role in drug development, for example in the field of antibiotics. A decrease in the discovery of novel leads from natural sources and the hope of finding new …
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Biosynthetic engineering of plantazolicin natural products
Plantazolicin (PZN) is a ribosomally synthesized and post-translationally modified peptide (RiPP) natural product that exhibits extraordinarily narrow-spectrum antibacterial activity towards the causative agent of anthrax, Bacillus anthracis. During PZN biosynthesis, a cyclodehydratase catalyzes …
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Mechanistic and synthetic studies on the prochlorosin and cytolysin families of lanthipeptides
… occupying a niche between small molecules and biologics. Research in the van der Donk lab focuses on lanthipeptides, a class of ribosomally synthesized and post-translationally modified peptides (RiPPs) that commonly feature antibacterial activity and contain the characteristic thioether …
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New Insights into Mycofactocin Biosynthesis, Structure and Function
<p>Mycofactocin is a putative ribosomally synthesized and post-translationally modified peptide (RiPP)-derived redox cofactor. Its biosynthesis is accomplished through the dedicated actions of the products of six conserved genes, <em>mftABCDEF</em>. The mycofactocin pathway is one of the most …
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Studies on the mechanism of action of the antimicrobial S-linked glycopeptide sublancin
… making it difficult to develop drugs with new and unique modes of action by generating analogs. Ribosomally synthesized and post-translationally modified peptide (RiPP) natural products are a rapidly expanding class of compounds with antimicrobial activity. Sublancin is one of five members of …
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