Lantibiotic mutants and chimeras of enhanced stability and activ

Chemistry: molecular biology and microbiology – Micro-organism – tissue cell culture or enzyme using process... – Recombinant dna technique included in method of making a...

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435325, 4352523, 4353201, 536 231, C12P 2106, C07H 1700

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active

061534056

ABSTRACT:
Nisin-subtilin mutant and chimeric prepeptides were constructed and expressed in a Bacillus subtilis strain that possesses all of the cellular machinery for making subtilin, except for the presubtilin gene. The chimera S.sub.L -Nis.sub.1-11 -Sub.sub.12-32 was prepared. The prepeptide has the subtilin leader sequence (S.sub.L), the N-terminal portion of the structural region was 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 (S.sub.L -Sub.sub.1-11 -Nis.sub.12-34) 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.

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