Nonribosomalpeptidesynthetases and their biotechnological potential in penicillium rubens Non-ribosomal peptide synthetases (NRPSs) are sophisticated, large multienzyme systems responsible for assembling a vast array of complex peptide natural products. Unlike ribosomal protein synthesis, which relies on messenger RNA templates, NRPSs operate independently, directly linking amino acids and other substrates to create molecules with significant structural diversity and potent biological activitiesNonribosomal Peptide Synthetase - an overview. These enzymes are crucial in microorganisms, serving as the biological machinery behind many compounds with applications in medicine and biotechnology作者：KAJ Bozhüyük·2024·被引用次数：60—Many clinically used drugs are derived from or inspired by bacterial natural products that often are produced throughnonribosomal peptide.... Understanding the structure and function of NRPSs is key to unlocking their potential for drug discovery and bioengineering.
NRPSs are characterized by their modular architecture, where each module is responsible for a specific step in the synthesis process. These modules are typically organized in a linear fashion and contain a series of functional domains that carry out distinct chemical transformations. The core domains include:
* Adenylation (A) domain: Selects and activates the specific amino acid or carboxylic acid substrate.
* Thiolation (T) or Peptidyl Carrier Protein (PCP) domain: Covalently binds the activated substrate via a phosphopantetheine arm.
* Condensation (C) domain: Catalyzes the formation of the peptide bond between the growing peptide chain and the newly activated substrate.
Additional domains, such as the N-methyltransferase (NMT) domain, Oxidation (O) domain, and Epimerization (E) domain, can be present to introduce modifications like methylation, oxidation, or stereochemical inversion, further expanding the chemical diversity of the resulting nonribosomal peptides (NRPs)作者：RD Süssmuth·2017·被引用次数：1045—Nonribosomal peptide synthetases (NRPSs) arelarge multienzyme machineries that assemble numerous peptideswith large structural and functional diversity.. The order and presence of these modules and domains dictate the final structure of the synthesized peptide作者：Z Li·2024·被引用次数：4—Nonribosomal peptide synthetases (NRPSs) aremultienzyme complexes that produce natural products(nonribosomal peptides, NRPs) with enormous chemical ....
The nonribosomal peptides synthesized by NRPSs exhibit an impressive range of biological activities, making them valuable targets for various applications. Many clinically important drugs, including antibiotics, antifungals, immunosuppressants, and anticancer agents, are derived from or inspired by these natural products.Evolution-inspired engineering of nonribosomal peptide ... For example, penicillin, a widely used antibiotic, is synthesized through a pathway involving NRPS-like enzymes. Other notable examples include vancomycin, daptomycin, and cyclosporine, all of which are produced by microorganisms and rely on NRPS machinery for their creation.
The inherent structural diversity and potent bioactivity of NRPs have spurred significant interest in their biotechnological potential. Researchers are actively exploring ways to engineer NRPS systems to produce novel peptides with tailored properties or to enhance the production of existing valuable compounds. This field of "evolution-inspired engineering" aims to leverage the natural biosynthetic capabilities of NRPSs for pharmaceutical and industrial purposes.
Despite their immense potential, studying and manipulating NRPSs presents several challenges. Their large size and complex modular structure can make them difficult to purify, crystallize, and characterize作者：RD Süssmuth·2017·被引用次数：1045—Nonribosomal peptide synthetases (NRPSs) arelarge multienzyme machineries that assemble numerous peptideswith large structural and .... Understanding the precise mechanisms of substrate selection, peptide bond formation, and product release requires sophisticated biochemical and structural biology techniques.
However, advancements in areas such as structural biology, genomics, and synthetic biology are continually expanding our understanding of NRPSsRefining and expanding nonribosomal peptide synthetase .... The visualization of key steps in NRPS function and the elucidation of their crystal structures are providing unprecedented insights into their catalytic mechanisms.作者：C Shi·2020·被引用次数：21—Nonribosomal peptide synthetases (NRPSs) are remarkable modular enzymes thatsynthesize peptide natural products. Furthermore, the identification and characterization of NRPS gene clusters in various organisms are revealing new pathways and novel peptide natural products.
The future of NRPS research holds great promise. Continued exploration of microbial diversity will undoubtedly uncover new NRPS systems and associated nonribosomal peptides with novel bioactivities.Nonribosomal peptide synthetases and their biotechnological ... Engineering these systems offers a powerful platform for the de novo design and synthesis of peptides with specific therapeutic or industrial applications, potentially leading to the development of next-generation pharmaceuticals and biomaterials.
Non-ribosomal peptide synthetases are essential molecular machines that enable the biosynthesis of a remarkable array of complex peptide natural products. Their modular design and diverse functional domains allow for the creation of molecules with significant structural complexity and a broad spectrum of biological activities, many of which are vital in medicine. As research continues to unravel the intricacies of NRPS function and structure, their role in drug discovery, biotechnology, and the broader field of natural product synthesis is poised to become even more significant.
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