This invention relates to novel recombinant botulinum neurotoxins serotype A exhibiting a higher thermostability and/or a higher oxidative resistance and/or higher stability against proteolytic degradation of the light chain and to methods for the manufacture of such recombinant botulinum neurotoxins. These novel recombinant botulinum neurotoxins comprise a modification of the light chain of the neurotoxin, and the methods comprise the steps of inserting mutations at the light chain in the nucleic acid sequence coding for a parental botulinum neurotoxin and expression of the recombinant nucleic acid sequence comprising the mutated sequence in a host cell. The invention further relates to novel recombinant single-chain precursor botulinum neurotoxins used in such methods, nucleic acid sequences encoding such recombinant single-chain precursor botulinum neurotoxins, and pharmaceutical compositions comprising the recombinant botulinum neurotoxin with a higher oxidative resistance and/or higher stability against proteolytic degradation of the light chain.
