Published: April 10, 2025

Proteins of the multinuclear non-heme iron-dependent oxidative (MNIO) enzyme superfamily catalyze various modification reactions on precursors ribosomally synthesized, post-translationally modified peptides (RiPPs). We recently identified two large families MNIO-modified RiPPs called bufferins, which enhance bacterial growth under copper stress by chelating excess metal ions. Here, we explored diversity potential MNIO substrates performing extensive _in silico_ studies. Analyses MNIO-coding biosynthetic gene clusters (BGCs) groups putative most are characterized specific Cys-containing motifs, throughout eubacterial phylogenetic tree. The harbor N-terminal Sec-dependent signal peptides, a rare feature among RiPPs. Some very long relative to those typical RiPPs, indicating that enzymes could modify both peptide and protein substrates. also distinct family integral membrane proteins with predicted extra-cytoplasmic domains mostly found in Actinomycetota, frequently but not systematically associated MNIOs. Most BGCs genes coding for DUF2063 domain-containing or structurally related proteins, serving as partners precursor modification. uncovered correlation between presence absence Sec types partner enzymes. This study depicts global landscape MNIO-dependent natural products unveiling genetically It reveals treasure trove new RiPP likely represent widespread strategy deal stress, other stresses, environments. IMPACT STATEMENT. belong an emerging oxidation synthesized (RiPP) precursors. largest involved homeostasis. In this work performed analyses explore major families. much larger than precursors, may proteins. defined subtypes enzymes’ dedicated Our unveiled functions beyond homeostasis, response stresses. will be basis investigations into undoubtedly lead discovery modifications functions.

Language: Английский