Botulinum neurotoxin homologs in non-Clostridium species

•We discovered the first homologs of botulinum neurotoxins outside of Clostridium.•The homologs are encoded in the genome of the food fermentation organism, Weissella oryzae S25.•The homologs represent two novel phylogenetic lineages of neurotoxin-related sequences. Clostridial neurotoxins (CNTs) are the deadliest toxins known and the causative agents of botulism and tetanus. Despite their structural and functional complexity, no CNT homologs are currently known outside Clostridium. Here, we report the first homologs of Clostridium CNTs within the genome of the rice fermentation organism Weissella oryzae SG25. One gene in W. oryzae S25 encodes a protein with a four-domain architecture and HExxH protease motif common to botulinum neurotoxins (BoNTs). An adjacent gene with partial similarity to CNTs is also present, and both genes seem to have been laterally transferred into the W. oryzae genome from an unknown source. Identification of mobile, CNT-related genes outside of Clostridium has implications for our understanding of the evolution of this important toxin family.