Lantibiotic mutants and chimeras of enhanced stability and activity, leader sequences therefor, genes encoding the same, and methods of producing and using the same

摘要

Nisin-subtilin mutant and chimeric pre-peptides were constructed and expressed in a Bacillus subtilis strain that possesses all of the cellular machinery for making subtilin, except for the pre-subtilin gene. The chimera SL-Nis1-11-Sub12-32 was prepared. This pre-peptide has the subtilin leader sequence (SL), the N-terminal portion of the structural region derived from nisin and the C-terminal portion of the structural region derived from subtilin. This chimera was accurately and efficiently converted to the mature lantibiotic, as demonstrated by a variety of physical and biological activity assays. In contrast, a SL-Sub1-11-Nis12-34 chimera was processed into a heterogeneous mixture of products, none of which appeared to be the correct chimeric lantibiotic. The mixture did, however, contain an active minor component with a biological activity that exceeded nisin itself.