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

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

机构地区：[1]Institute for Molecular Bio Science,Goethe University Frankfurt,60438,Frankfurt am Main,Germany [2]LOEWE Center for Translational Biodiversity Genomics(TBG),60325,Frankfurt am Main,Germany

出　　处：《Synthetic and Systems Biotechnology》2022年第1期631-647,共17页合成和系统生物技术（英文）

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

摘　　要：Complex peptide natural products exhibit diverse biological functions and a wide range of physico-chemical properties.As a result,many peptides have entered the clinics for various applications.Two 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 routes.These 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 peptides.In this review,we contrast the key principles of both biosynthetic routes and compare the different biochemical strategies to install the most frequently encountered peptide modifications.In addition,the influence of the fundamentally different biosynthetic principles on past,current and future engineering ap-proaches is illustrated.Despite the different biosynthetic principles of both peptide biosynthetic routes,the arsenal of characterized peptide modifications encountered in RiPP and NRPS systems is largely overlapping.The 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.

关 键 词：Peptide natural products Non-ribosomal peptide synthetases Ribosomally synthesized and post-translationally modified peptides BIOSYNTHESIS Modification Engineering 

分 类 号：O63[理学—高分子化学]