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4,5 Both hard copy thesis and e-thesis No This thesis is due for publication or the author is actively seeking to publish this material Hill, Colin Cotter, Paul D. Ross, R. Paul Healy, Brian Department of Agriculture, Food and the Marine, Ireland Teagasc 2016-06-03T15:01:24Z 2014 2014 The bacteriocin class of antimicrobial peptides have emerged as a viable alternative to at least partially fill the void created by the end of the golden age of antibiotic discovery. Along with this potential use in a clinical setting, bacteriocins also play an important role as bio-preservatives in the food industry. This thesis focuses on a specific bacteriocin group, the lantibiotics (Lanthionine-containing antibiotics). Their numerous methods of appliance in a food setting and how their gene-encoded nature can be modified to improve on overall bioactivity and functionality are explored here. The use of a lantibiotic (lacticin 3147) producing starter culture to control the Crohn’s disease-linked pathogen Mycobacterium paratuberculosis was assessed in a raw milk cheese. Although lacticin 3147 production did not effectively control the pathogen, the study provided an impetus to employ a variety of PCR-based mutagenesis techniques with a view to the creation of enhanced lantibiotic derivatives. Through the use of these techniques, a number of enhanced derivatives were generated from the ‘hinge’ region of the nisin peptide. Furthermore, a derivative in which the three hinge amino acids were replaced with three alanines represents the first enhanced derivative of nisin to have been designed through a rational process. This derivative also formed the backbone for the creation of an active, trypsin resistant, variant. Through the employment of further mutagenesis methods a derivative was created with potential use as an oral anti-bacterial in the future. Finally a number of lead nisin derivatives were investigated to assess their anti- Streptococcus agalactiae ability, a mastitis associated pathogen. Also a system was developed to facilitate the large scale production of these candidates, or other nisin derivatives, from dairy substrates. Department of Agriculture, Food and the Marine, Ireland (Food Institutional Research Measure (08/RD/C/691)) Not peer reviewed Accepted Version application/pdf Healy, B. C. 2014. Bioengineering of nisin to enhance functionality against dairy pathogens. PhD Thesis, University College Cork. 163 https://hdl.handle.net/10468/2696 en University College Cork © 2014, Brian C. Healy http://creativecommons.org/licenses/by-nc-nd/3.0/ Nisin Lacticin 3147 Bacteriocin Lantibiotic Mutagenesis Bioengineering Streptococcus agalactiae Mycobacterium avium subspecies paratuberculosis Lactococcus lactis false Bioengineering of nisin to enhance functionality against dairy pathogens Doctoral thesis Doctoral PhD (Science) c.hill@ucc.ieinfo:eu-repo/semantics/openAccess