Complex peptide natural products: biosynthetic principles, challenges and opportunities for pathway engineering
- 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 approaches 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.
Author: | Sebastian Leonhard WenskiGND, Sirinthra Thiengmag, Eric J. N. HelfrichORCiDGND |
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URN: | urn:nbn:de:hebis:30:3-734982 |
DOI: | https://doi.org/https://doi.org/10.1016/j.synbio.2022.01.007 |
ISSN: | 2405-805X |
Parent Title (English): | Synthetic and systems biotechnology |
Publisher: | Ke Ai ; Elsevier |
Place of publication: | Beijing ; Amsterdam |
Document Type: | Article |
Language: | English |
Date of Publication (online): | 2022/02/09 |
Date of first Publication: | 2022/02/09 |
Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
Release Date: | 2023/04/04 |
Tag: | Biosynthesis; Engineering; Modification; Non-ribosomal peptide synthetases; Peptide natural products; Ribosomally synthesized and post-translationally modified peptides |
Volume: | 7 |
Issue: | 1 |
Page Number: | 17 |
First Page: | 631 |
Last Page: | 647 |
Note: | The authors gratefully acknowledge funding by the LOEWE Center for Translational Biodiversity Genomics (LOEWE-TBG). |
HeBIS-PPN: | 508980372 |
Institutes: | Biowissenschaften |
Dewey Decimal Classification: | 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
Sammlungen: | Universitätspublikationen |
Licence (German): | Creative Commons - CC BY-ND - Namensnennung - Keine Bearbeitungen 4.0 International |