TY  - JOUR
A1  - Baunach, Martin
A1  - Chowdhury, Somak
A1  - Stallforth, Pierre
A1  - Dittmann-Thünemann, Elke
T1  - The landscape of recombination events that create nonribosomal peptide diversity
JF  - Molecular biology and evolution : MBE
N2  - 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.
KW  - evolution
KW  - recombination
KW  - structural diversity
KW  - natural products
KW  - nonribosomal peptide synthetases
KW  - microbial ecology
Y1  - 2021
U6  - https://doi.org/10.1093/molbev/msab015
SN  - 0737-4038
SN  - 1537-1719
VL  - 38
IS  - 5
SP  - 2116
EP  - 2130
PB  - Oxford Univ. Press
CY  - Oxford
ER  -