Non ribosomalpeptidesynthetases nrps Nonribosomal peptide synthetases (NRPSs) are remarkable, large multienzyme machineries that play a critical role in the biosynthesis of a vast array of complex peptide natural products.作者：BR Miller·2016·被引用次数：211—Thenon-ribosomal peptidesynthetases are modular enzymes that catalyze synthesis of important peptide products from a variety of standard and non-proteinogenic ... Unlike ribosomal protein synthesis, which relies on messenger RNA templates, NRPSs operate as sophisticated molecular assembly lines, directly synthesizing peptides from a variety of standard and non-proteinogenic amino acids. These enzymes are crucial for producing secondary metabolites with diverse and significant biological activities, making them important targets in fields ranging from drug discovery to industrial biotechnology. Understanding the intricate structure and function of NRPSs is key to unlocking their full potential.Genome mining unearths a hybrid nonribosomal peptide ...
The defining characteristic of nonribosomal peptide synthetases is their modular structure. Each NRPS is typically composed of a series of repeating modules, with each module responsible for incorporating a specific amino acid or other acyl substrate into the growing peptide chain. This modularity allows for immense flexibility and diversity in the final peptide product.作者：KAJ Bozhüyük·2024·被引用次数：60—Bacterial NPs, especially those derived fromnonribosomal peptide syn- thetases (NRPSs), have emerged as ideal targets for synthetic biology and ... Within a typical module, core catalytic domains are present, including:
* Adenylation (A) domain: This domain is responsible for selecting and activating the specific amino acid substrate using ATPNon-ribosomal peptide synthetases.
* Thiolation (T) or Peptidyl Carrier Protein (PCP) domain: This domain binds the activated amino acid via a phosphopantetheine arm.
* Condensation (C) domain: This domain catalyzes the formation of the peptide bond between the activated amino acid on the current module's T domain and the growing peptide chain attached to the previous module's T domain.
Additional domains can also be present within modules or at the termini of the NRPS complex, such as acyltransferase (AT) domains for incorporating extender units, epimerization (E) domains for altering the stereochemistry of amino acids, and thioesterase (TE) domains for releasing the completed peptide, often leading to cyclization or other modifications.Non-ribosomal peptides (NRPs) aresmall, secondary metabolites not produced by the ribosomebut by specialized enzymes called non-ribosomal peptide synthetases ... This assembly-line process, where each module adds a specific building block, enables the synthesis of peptides with complex structures, including cyclic and branched forms, and the incorporation of unusual amino acids not found in proteins synthesized by ribosomesThese peptidic natural products are assembled by large enzymes, referred to asnonribosomal peptide synthetases... endogenous aminoacyl-tRNA synthetase, the tRNA ....
The synthesis catalyzed by nonribosomal peptide synthetases results in nonribosomal peptides (NRPs), which are secondary metabolites with a broad spectrum of biological activities. These include potent antibiotics, antifungals, immunosuppressants, and toxins.作者：MA Martínez-Núñez·2016·被引用次数：169—NRPSs are defined asmultimodular enzymes, consisting of repeated modules. The NRPS enzymes are at operons and their regulation can be positive ... The structural diversity of NRPs is immense, stemming from the combinatorial possibilities offered by the modular nature of NRPSs, the wide range of available amino acid and extender substrates, and the action of modifying domains.作者：BR Miller·2016·被引用次数：211—Thenon-ribosomal peptidesynthetases are modular enzymes that catalyzesynthesisof important peptide products from a variety of standard and non-proteinogenic ...
Microorganisms, particularly bacteria and fungi, are the primary producers of nonribosomal peptides. The genes encoding NRPS enzymes are often clustered together in operons, allowing for coordinated expression and regulation. This genetic encoding provides a blueprint for the assembly of these complex molecules. The inherent flexibility of NRPS systems has also made them attractive targets for bioengineering. Researchers are exploring ways to modify the modularity and domain composition of NRPSs to create novel peptides with tailored properties, a field often referred to as "evolution-inspired engineering" or synthetic biology approaches.Nonribosomal Peptide Synthesis—Principles and Prospects
The valuable biological activities of nonribosomal peptides have led to their significant exploitation in medicine and industry.作者：GL Challis·2000·被引用次数：1016—Nonribosomal peptide synthetases (NRPSs) are large modular proteins thatselectively bind, activate and condense amino acidsin an ordered manner. Many clinically important drugs, such as the antibiotic vancomycin and the immunosuppressant cyclosporine, are nonribosomal peptides. The ongoing exploration of microbial genomes and the development of advanced bioengineering techniques are continuously uncovering new NRPS systems and novel NRPs with potential therapeutic applications.
Furthermore, the ability to reprogram NRPSs opens exciting avenues for the de novo design and production of peptide-based natural products for drug discovery and other applications. By understanding the structure, function, and dynamics of these large enzymatic complexes, scientists can refine and expand their capabilities, leading to the generation of valuable compounds that would be difficult or impossible to synthesize through conventional chemical methods. The study of nonribosomal peptide synthetases continues to be a dynamic and fertile area of research, promising further breakthroughs in natural product discovery and biotechnology.
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