Bioengineering of the lantibitoic nisin to create new antimicrobial functionalities

Liang Zhou

Research output: ThesisThesis fully internal (DIV)

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The resistance of pathogens to traditional antibiotics enforces people to search for new antimicrobial agents. Lantibiotics are ribosomally synthesized and posttranslationally modified peptides. They can efficiently inhibit the growth of Gram-positive bacteria, by binding to lipid II and forming pores in the membrane. Nisin is the prototype of lantibiotic. It binds to lipid II with the first two rings and the C-terminus will bend into the membrane and form a pore complex together with lipid II. In this thesis, nisin was engineered in different ways to create peptides with new functionalities. The hinge region, which is the most flexible region of nisin, was varied to different lengths and the antimicrobial activity showed that shortening the hinge region is detrimental for the activity, while elongation it with one or two amino acid residues reduced the activity only modestly. To potentiate the inhibition efficiency of nisin against Gram-negative pathogens, different anti-Gram-negative peptides were attached to nisin. The fusion consisting of nisin and part of apidaecin displayed twice as high activity than nisin against Escherichia coli. Three different tryptophan analogues were successfully incorporated into nisin by constructing an incorporation and production system in Lactococcus lactis. The nisin variants containing 5-hydroxyl Trp showed a new biochemical character. Furthermore, the complex of NisB and prenisin was purified and characterized for cryo-EM analysis. This thesis highlights the great potential of bioengineering lantibiotics to become an effective agent, e.g. in the gut of humans, to fight infections.
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
  • University of Groningen
  • Kuipers, Oscar, Supervisor
Award date9-May-2016
Place of Publication[Groningen
Print ISBNs978-90-367-8777-2
Electronic ISBNs978-90-367-8776-5
Publication statusPublished - 2016

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