Class B enzymes belong to the large superfamily of metallo-β-lactamase fold proteins. ... Class B enzymes, presenting an archaic fold, are widely ...SkiptomaincontentThankyouforvisitingnature.com.YouareusingabrowserversionwithlimitedsupportforCSS.Toobtainthebestexperience,werecommendyouuseamoreuptodatebrowser(orturnoffcompatibilitymodeinInternetExplorer).Inthemeantime,toensurecontinuedsupport,wearedisplayingthesitewithoutstylesandJavaScript.AdvertisementnaturescientificreportsarticlesarticleHumanmetallo-β-lactamaseenzymesdegradepenicillinDownloadPDFSubjectsClinicalmicrobiologyGeneticsresearchAbstractNonribosomalpeptidesareassemblages,includingantibiotics,ofcanonicalaminoacidsandothermolecules.β-lactamantibioticsactonbacterialcellwallsandcanbecleavedbyβ-lactamases.β-lactamaseactivityinhumanshasbeenneglected,eventhougheighteenenzymeshavealreadybeenannotatedsuchinhumangenome.Theirhydrolysisactivitiesonantibioticshavenotbeenpreviouslyinvestigated.Here,wereportthathumancellswereabletodigestpenicillinandthisactivitywasinhibitedbyβ-lactamaseinhibitor,i.e.sulbactam.PenicillindegradationinhumancellswasmicrobiologicallydemonstratedonPneumococcus.WeexpressedaMBLAC2humanβ-lactamase,knownasanexosomebiogenesisenzyme.Itcleavedpenicillinandwasinhibitedbysulbactam.Finally,β-lactamasesarewidelydistributed,archaic,andhavewidespectrum,includingdigestinganticancerandβ-lactams,thatcanbethenusedasnutriments.TheevidenceoftheotherMBLAC2roleasabonafideβ-lactamaseallowsforreassessmentofβ-lactamsandβ-lactamasesroleinhumans.DownloadPDFIntroductionNonribosomalpeptidesandpolyketidesynthasesareassemblagesofaminoacidsandothermoleculesthatmayreflectthepre-ribosomalsynthesisofpeptides.Firstidentifiedinfungiandbacteriaandthenusedasantibiotics1oranticancerdrugs,itisnowpossibletoidentifytheminmostlivingorganisms;evenspringtailhexapodssecretepenicillin2.Aspartofourworksonantibioticresistance,wehavepreviouslydemonstratedthatancientβ-lactamasereconstitutedfrommetagenomicdatasetscanbeeffectiveoncurrentantib