Complex peptide natural products: Biosynthetic principles, challenges and opportunities for pathway engineering

作     者：Sebastian L.Wenski Sirinthra Thiengmag Eric J.N.Helfrich 

作者机构：Institute for Molecular Bio ScienceGoethe University Frankfurt60438Frankfurt am MainGermany LOEWE Center for Translational Biodiversity Genomics(TBG)60325Frankfurt am MainGermany 

出 版 物：《Synthetic and Systems Biotechnology》 (合成和系统生物技术（英文）)

年 卷 期：2022年第7卷第1期

页      面：631-647页

核心收录：

学科分类：081704[工学-应用化学] 07[理学] 08[工学] 0817[工学-化学工程与技术] 070305[理学-高分子化学与物理] 080501[工学-材料物理与化学] 0805[工学-材料科学与工程（可授工学、理学学位）] 0703[理学-化学] 

基　　金：the LOEWE Center for Translational Biodiversity Genomics(LOEWE-TBG) 

主　　题：Peptide natural products Non-ribosomal peptide synthetases Ribosomally synthesized and post-translationally modified peptides Biosynthesis Modification Engineering 

摘      要：Complex peptide natural products exhibit diverse biological functions and a wide range of physico-chemical *** a result,many peptides have entered the clinics for various *** main routes for the biosynthesis of complex peptides have evolved in nature:ribosomally synthesized and post-translationally modified peptide(RiPP)biosynthetic pathways and non-ribosomal peptide synthetases(NRPSs).Insights into both bioorthogonal peptide biosynthetic strategies led to the establishment of universal principles for each of the two *** universal rules can be leveraged for the targeted identification of novel peptide biosynthetic blueprints in genome sequences and used for the rational engineering of biosynthetic pathways to produce non-natural *** this review,we contrast the key principles of both biosynthetic routes and compare the different biochemical strategies to install the most frequently encountered peptide *** addition,the influence of the fundamentally different biosynthetic principles on past,current and future engineering ap-proaches is *** the different biosynthetic principles of both peptide biosynthetic routes,the arsenal of characterized peptide modifications encountered in RiPP and NRPS systems is largely *** continuous expansion of the biocatalytic toolbox of peptide modifying enzymes for both routes paves the way towards the production of complex tailor-made peptides and opens up the possibility to produce NRPS-derived peptides using the ribosomal route and vice versa.