Engineering of Bacillus subtilis 168 for Increased Nisin Resistance

Nisin is a natural bacteriocin produced commercially by Lactococcus lactis and widely used in the food industry as a preservative because of its broad host spectrum. Despite the low productivity and troublesome fermentation of L. lactis, no alternative cost-effective host has yet been found. Bacillu...

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Bibliographic Details
Published in:Applied and Environmental Microbiology 2009-11, Vol.75 (21), p.6688-6695
Main Authors: Hansen, Mette E, Wangari, Romilda, Hansen, Egon B, Mijakovic, Ivan, Jensen, Peter R
Format: Article
Language:English
Subjects:
Anti-Bacterial Agents - pharmacology
Bacillus subtilis
Bacillus subtilis - chemistry
Bacillus subtilis - drug effects
Bacillus subtilis - genetics
Bacteriocins
Biological and medical sciences
Biotechnology
Drug Resistance, Bacterial
Fermentation
Fundamental and applied biological sciences. Psychology
Gene expression
Gene Expression Profiling
Genetic Engineering
Gram-positive bacteria
Lactococcus lactis - genetics
Lactococcus lactis - metabolism
Microbiology
Nisin - pharmacology
Proteome - analysis
Stress, Physiological
Studies
Toxins
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Summary:Nisin is a natural bacteriocin produced commercially by Lactococcus lactis and widely used in the food industry as a preservative because of its broad host spectrum. Despite the low productivity and troublesome fermentation of L. lactis, no alternative cost-effective host has yet been found. Bacillus subtilis had been suggested as a potential host for the biosynthesis of nisin but was discarded due to its sensitivity to the lethal action of nisin. In this study, we have reevaluated the potential of B. subtilis as a host organism for the heterologous production of nisin. We applied transcriptome and proteome analyses of B. subtilis and identified eight genes upregulated in the presence of nisin. We demonstrated that the overexpression of some of these genes boosts the natural defenses of B. subtilis, which allows it to sustain higher levels of nisin in the medium. We also attempted to overcome the nisin sensitivity of B. subtilis by introducing the nisin resistance genes nisFEG and nisI from L. lactis under the control of a synthetic promoter library.
ISSN:0099-2240
1098-5336
1098-6596
DOI:10.1128/AEM.00943-09