The landscape of recombination events that create nonribosomal peptide diversity
- Nonribosomal peptides (NRP) are crucial molecular mediators in microbial ecology and provide indispensable drugs. Nevertheless, the evolution of the flexible biosynthetic machineries that correlates with the stunning structural diversity of NRPs is poorly understood. Here, we show that recombination is a key driver in the evolution of bacterial NRP synthetase (NRPS) genes across distant bacterial phyla, which has guided structural diversification in a plethora of NRP families by extensive mixing andmatching of biosynthesis genes. The systematic dissection of a large number of individual recombination events did not only unveil a striking plurality in the nature and origin of the exchange units but allowed the deduction of overarching principles that enable the efficient exchange of adenylation (A) domain substrates while keeping the functionality of the dynamic multienzyme complexes. In the majority of cases, recombination events have targeted variable portions of the A(core) domains, yet domain interfaces and the flexible A(sub)Nonribosomal peptides (NRP) are crucial molecular mediators in microbial ecology and provide indispensable drugs. Nevertheless, the evolution of the flexible biosynthetic machineries that correlates with the stunning structural diversity of NRPs is poorly understood. Here, we show that recombination is a key driver in the evolution of bacterial NRP synthetase (NRPS) genes across distant bacterial phyla, which has guided structural diversification in a plethora of NRP families by extensive mixing andmatching of biosynthesis genes. The systematic dissection of a large number of individual recombination events did not only unveil a striking plurality in the nature and origin of the exchange units but allowed the deduction of overarching principles that enable the efficient exchange of adenylation (A) domain substrates while keeping the functionality of the dynamic multienzyme complexes. In the majority of cases, recombination events have targeted variable portions of the A(core) domains, yet domain interfaces and the flexible A(sub) domain remained untapped. Our results strongly contradict the widespread assumption that adenylation and condensation (C) domains coevolve and significantly challenge the attributed role of C domains as stringent selectivity filter during NRP synthesis. Moreover, they teach valuable lessons on the choice of natural exchange units in the evolution of NRPS diversity, which may guide future engineering approaches.…
Author details: | Martin BaunachORCiDGND, Somak ChowdhuryORCiDGND, Pierre StallforthORCiDGND, Elke Dittmann-ThünemannORCiDGND |
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DOI: | https://doi.org/10.1093/molbev/msab015 |
ISSN: | 0737-4038 |
ISSN: | 1537-1719 |
Pubmed ID: | https://pubmed.ncbi.nlm.nih.gov/33480992 |
Title of parent work (English): | Molecular biology and evolution : MBE |
Publisher: | Oxford Univ. Press |
Place of publishing: | Oxford |
Publication type: | Article |
Language: | English |
Date of first publication: | 2021/05/01 |
Publication year: | 2021 |
Release date: | 2023/10/20 |
Tag: | evolution; microbial ecology; natural products; nonribosomal peptide synthetases; recombination; structural diversity |
Volume: | 38 |
Issue: | 5 |
Number of pages: | 15 |
First page: | 2116 |
Last Page: | 2130 |
Funding institution: | Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) German Research Foundation (DFG) [239748522-SFB 1127]; DFG German Research Foundation (DFG) European Commission [RTG 2473]; Leibniz Association; Werner Siemens Stiftung |
Organizational units: | Mathematisch-Naturwissenschaftliche Fakultät / Institut für Biochemie und Biologie |
DDC classification: | 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
Peer review: | Referiert |
Publishing method: | Open Access / Gold Open-Access |
DOAJ gelistet | |
License (German): | CC-BY - Namensnennung 4.0 International |