Nisin M: a bioengineered Nisin A variant that retains full induction capacity but has significantly reduced antimicrobial activity

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dc.contributor.authorO'Connor, Michelle
dc.contributor.authorField, Des
dc.contributor.authorGrainger, Aoife
dc.contributor.authorO'Connor, Paula M.
dc.contributor.authorDraper, Lorraine A.
dc.contributor.authorRoss, R. Paul
dc.contributor.authorHill, Colin
dc.contributor.funderScience Foundation Irelanden
dc.contributor.funderSociety for Applied Microbiologyen
dc.date.accessioned2021-11-10T09:06:01Z
dc.date.available2021-11-10T09:06:01Z
dc.date.issued2020-07-20
dc.date.updated2021-11-10T08:56:44Z
dc.description.abstractNisin A is a potent antimicrobial with potential as an alternative to traditional antibiotics, and a number of genetically modified variants have been created that target clinically relevant pathogens. In addition to antimicrobial activity, nisin autoregulates its own production via a signal transduction pathway, a property that has been exploited in a protein expression system termed the nisin-controlled gene expression (NICE) system. Although NICE has become one of the most popular protein expression systems, one drawback is that the inducer peptide, nisin A, also has inhibitory activity. It has already been demonstrated that the N-terminal region of nisin A contributes to antimicrobial activity and signal transduction properties; therefore, we conducted bioengineering of nisin at positions Pro9 and Gly10 within ring B to produce a bank of variants that could potentially be used as alternative induction peptides. One variant, designated nisin M, has threonines at positions 9 and 10 and retains induction capacity comparable to that of wild-type nisin A, while most of the antimicrobial activity is abolished. Further analysis confirmed that nisin M produces a mix of peptides as a result of different degrees of dehydration of the two threonines. We show that nisin M exhibits potential as a more suitable alternative to nisin A for the expression of proteins that may be difficult to express or for production of proteins in strains that are sensitive to wild-type nisin. Moreover, it may address the increasing demand by industry for optimization of peptide fermentations to increase yields or production rates.IMPORTANCE This study describes the generation of a nisin variant with superior characteristics for use in the NICE protein expression system. The variant, termed nisin M, retains an induction capacity comparable to that of wild-type nisin A but exhibits significantly reduced antimicrobial activity and can therefore be used at concentrations that are normally toxic to the expression host.en
dc.description.sponsorshipScience Foundation Ireland (SFI/12/RC/2273 P2); Society for Applied Microbiology (Students into Work Grant)en
dc.description.statusPeer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.articleide00984-20en
dc.identifier.citationO'Connor, M., Field, D., Grainger, A., O'Connor, P. M., Draper, L., Ross, R. P. and Hill, C. (2020) 'Nisin M: a bioengineered Nisin A variant that retains full induction capacity but has significantly reduced antimicrobial activity', Applied and Environmental Microbiology, 86(15), e00984-20 (13pp). doi: 10.1128/AEM.00984-20en
dc.identifier.doi10.1128/AEM.00984-20en
dc.identifier.eissn1098-5336
dc.identifier.endpage13en
dc.identifier.issn0099-2240
dc.identifier.issued15en
dc.identifier.journaltitleApplied and Environmental Microbiologyen
dc.identifier.startpage1en
dc.identifier.urihttps://hdl.handle.net/10468/12183
dc.identifier.volume86en
dc.language.isoenen
dc.publisherAmerican Society for Microbiologyen
dc.relation.projectinfo:eu-repo/grantAgreement/SFI/SFI Technology and Innovation Development Award (TIDA) - Training Award/10/IN.1/B3027 TIDA Training 11/IE/Lantibiotics: the next generation/en
dc.relation.projectinfo:eu-repo/grantAgreement/SFI/SFI Research Centres/12/RC/2273/IE/Alimentary Pharmabiotic Centre (APC) - Interfacing Food & Medicine/en
dc.rights© 2020, American Society for Microbiology. All Rights Reserved.en
dc.subjectAntimicrobial activityen
dc.subjectAutoinductionen
dc.subjectLactococcus lactisen
dc.subjectNisinen
dc.subjectProtein expressionen
dc.subjectSignal transductionen
dc.titleNisin M: a bioengineered Nisin A variant that retains full induction capacity but has significantly reduced antimicrobial activityen
dc.typeArticle (peer-reviewed)en
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