Optimization of critical medium components for enhancing antibacterial thiopeptide nocathiacin I production with significantly improved quality

(整期优先)网络出版时间:2017-04-14
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NocathiacinI,aglycosylatedthiopeptideantibiotic,displaysexcellentantibacterialactivitiesagainstmultidrugresistantbacterialpathogens.Previously,anovelnocathiacinIformulationforintravenousadministrationhasbeensuccessfullydevelopedanditsaqueoussolubilityisgreatlyenhancedforclinicalapplication.ThepurposeofthepresentstudywastoincreasethefermentationtiterofnocathiacinIandreduceoreliminateanalogousimpuritiesbyscreeningthemediumingredientsusingresponsesurfacemethodology.Afterasysmaticoptimization,awater-solublemediumcontainingquality-controllablecomponentswasdevelopedandvalidated,resultinginanincreaseintheproductionofnocathiacinIfrom150to405.8mg·L-1at150-Lscale.Meanwhile,theanalogousimpuritiesexistedinreportedprocessesweregreatlyreducedoreliminated.Usingoptimizedmediumforfermentation,nocathiacinIwithpharmaceuticallyacceptablequalitywaseasilyobtainedwitharecoveryof67%.Inconclusion,theresultsfromthepresentstudyofferapracticalandefficientfermentationprocessfortheproductionofnocathiacinIasatherapeuticagent.