Natural diversifying evolution of nonribosomal peptide synthetases in a defensive symbiont reveals nonmodular functional constraints.

ABSTRACT: The modular architecture of nonribosomal peptide synthetases (NRPSs) has inspired efforts to study their evolution and engineering. In this study, we analyze in detail a unique family of NRPSs from the defensive intracellular bacterial symbiont, Candidatus Endobryopsis kahalalidifaciens (Ca. E. kahalalidifaciens). We show that intensive and indiscriminate recombination events erase trivial sequence covariations induced by phylogenetic relatedness, revealing nonmodular functional constraints and clear recombination units. Moreover, we reveal unique substrate specificity determinants for multiple enzymatic domains, allowing us to accurately predict and experimentally discover the products of an orphan NRPS in Ca. E. kahalalidifaciens directly from environmental samples o

SUBMITTER: Li Z 

PROVIDER: S-EPMC11428043 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature