SCIENCE: Evolutionary Project of Non -Non -Non -Non -nucleic peptide synthetic enzyme

4 min read

  

Natural products (NP) play a key role in drug discovery. Nearly half of the newly developed drugs in the past 40 years originated from natural products.However, the complex structure of natural products has made it converted into a major challenge for clinical drugs, especially in chemical derivatives or full synthesis, especially large -scale synthesis.This complexity limits the study of structure-active relationship, which hinders the development of clue drugs based on natural products.


Non -nucleosogype peptidase (NRPS):


Natural products in bacteria are usually derived from non -ribosomal peptide synthetase (NRPS). Non -nucleosogyl peptide synthesis enzymes have become ideal targets for synthetic biology.Non -nucleosogylase synthesis is actually a large enzyme complex. It is responsible for synthesizing a variety of non -ribin peptides (NRP), and even clinical drugs, such as penicillin, bolterromycin, and cyclopylin.These enzyme complexes are composed of multiple enzyme domain modules, and each module -enzyme activity center (such as adenohide domain, sulfurization domain, synthesis domain, etc.) catalyzed specific chemical reactionsModules, gradually constructing peptide chains and chemical modification, and release mature peptides at appropriate time.


Non -Non -Non -nucleic peptide synthesisEvolutionThe
The logic of this assembly mechanism has stimulated the attempts of researchers to design large -scale synthetic enzymes to produce natural product simulation.The latest progress of technical and structural data, the continuous growth of open genome data, and the efforts to develop the processing tools of biological synthetic gene clusters (BGC) and identifying natural molecules, which accelerates the development of the innovative biological strategy of large synthetic enzyme engineering.Understanding the evolution mechanism of these huge multi -functional enzyme machines can enhance our ability to redesign the protein of protein and achieve greater structural diversity while maintaining high production. Therefore, it is possible to expand our therapeutic molecular library.


The evolution of NRPS involves genetic reorganization, species formation, horizontal gene transfer and other processes.In particular, sub -domain exchange in NRPS (responsible for selecting and activating the extension unit) of NRPS is the key driving force for NRP diversity.This seed domain exchange allows NRPS to adapt to new functions, thereby synthesizing new peptide compounds.


Challenges and opportunities for synthetic biology and genetic engineering:
Although NRPS has huge potential in synthetic biology, the complex compounds of design and engineering are still challenging.In order to overcome these challenges, the researchers have developed new strategies, such as the XUT (exchange unit) method. This method imitates the genetic reorganization event in natural evolution, redesign NRPS by synthetic biology meansEssenceThe engineering exchange unit method has expanded structure diversity and surpassed the limitations of natural diversity.The XUT method can effectively change the assembly line after the T domain to the assembly lines outside the C domain. If the enzyme domain is inserted, it is proven, and the XU and XUC methods that previously introduced the repetition of the NRPS module were introduced before.


Implementation and verification of the XUT method:
The XUT method is designed to design new biological synthesis pathways by identifying possible reorganization sites in NRPs.This method can not only introduce new chemical functions, but also reorganize between different NRPS modules, thereby creating enzymes with new functions.In the article, the effectiveness of the XUT method is verified by designing the inhibitors of the protease body, and a peptide compound with biological activity is successfully synthesized.



The picture is from the original text, provided by the author



in conclusion
The
The text introduces the importance of natural products in drug discovery, and the application and challenges of NRPS in synthetic biology.The article emphasizes that through synthetic biology and genetic engineering methods, especially the XUT method, it can not only imitate the reorganization events in natural evolution, but also surpass the limitations of natural diversity.Enzymes synthesize custom peptides with specific biological activity, which provides new ways for drug discovery and biological activated compounds.

You May Also Like

More From Author