There are seven serotypes of Botulinum Neurotoxins (BoNTs) produced by various strains of Clostridium botulinum. BoNTs are synthesized as inactive single chain protein precursors and activated by proteolytic cleavage to generate disulfide-linked two-chain proteins. The 50 kDa light chain contains the catalytic domain, whereas the 100 kDa heavy chain contains an internal translocation domain and a receptor binding domain. BoNTs are the most potent protein toxins for humans. As zinc proteases, they cleave SNARE proteins to elicit flaccid paralysis in botulism by blocking acetylcholine release at the neuromuscular junction.
E. coli-expressed recombinant BoNT light chains are active proteases. However, they are not toxic because they cannot enter into host cells in the absence of the heavy chains.
