Abstract
Nisin is an important antimicrobial peptide that has enormous applications in biotechnology. Despite many encouraging efforts, its overproduction has been a long-standing challenge due to the complexity of the underlying pathway and the difficulty in genetic modification of lactic acid bacteria. Here, we cloned an entire nisin biosynthesis pathway from a nisin-producing strain (Lactococcus lactis K29) into a plasmid and transplanted the plasmid into a nisin deficient strain Lactococcus lactis MG1363, resulting in successful heterologous expression of bioactive recombinant nisin. To increase nisin harvest, we also overexpressed nisA, a gene responsible for nisin precursor production, with a set of constitutive promoters. To further optimize nisin yield, we minimized the metabolic cost of the engineered strains by integrating nisA overexpression cassettes and the recombinant pathway into a single circuit. With our rational construction and optimization, our engineered optimized strain is able to produce bioactive nisin with a yield of 1098 IU/mL, which is more than six times higher than that of the original strain.
Original language | English (US) |
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Pages (from-to) | 439-445 |
Number of pages | 7 |
Journal | ACS synthetic biology |
Volume | 3 |
Issue number | 7 |
DOIs | |
State | Published - Jul 18 2014 |
Keywords
- lactic acid bacteria
- nisin biosynthesis
- optimization
- pathway engineering
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology (miscellaneous)
- Biomedical Engineering