The Landscape of Recombination Events That Create Nonribosomal Peptide Diversity.
evolution
microbial ecology
natural products
nonribosomal peptide synthetases
recombination
structural diversity
Journal
Molecular biology and evolution
ISSN: 1537-1719
Titre abrégé: Mol Biol Evol
Pays: United States
ID NLM: 8501455
Informations de publication
Date de publication:
04 05 2021
04 05 2021
Historique:
pubmed:
23
1
2021
medline:
20
7
2021
entrez:
22
1
2021
Statut:
ppublish
Résumé
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 and matching 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 Acore domains, yet domain interfaces and the flexible Asub 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.
Identifiants
pubmed: 33480992
pii: 6108112
doi: 10.1093/molbev/msab015
pmc: PMC8097286
doi:
Substances chimiques
Peptide Synthases
EC 6.3.2.-
non-ribosomal peptide synthase
EC 6.3.2.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2116-2130Informations de copyright
© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.
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